Copper(I)-Photocatalyzed Diastereoselective Aziridination of N-Sulfonyl Imines with Vinyl Azides: Application to Benzo[f][1,2,3]oxathiazepines Dioxides and Fused Isoxazolines.

An in situ generated photoactive copper(I)-complex-catalyzed aziridination reaction of cyclic N-sulfonyl imines with α-aryl-substituted vinyl azides irradiated by blue-LEDs light is reported for the first time. This novel SET process represents a mild, sustainable, and pragmatic method for accessing synthetically resourceful sulfamidate-fused aziridines in acceptable chemical yields with excellent diastereoselectivities. Delightedly, pharmacologically attractive benzo[f][1,2,3]oxathiazepine dioxides and fused isoxazoline frameworks were achieved through our newly developed metal-free based ring-expansion techniques, highlighting the synthetic value of accessed aziridines. Finally, the possible mechanism for [2+1] aza-cyclization was presented based on the conduction of a series of control experiments.

Oral metronomic chemotherapy after definitive chemoradiation in esophageal squamous cell carcinoma: a randomized clinical trial.

BACKGROUND: Improving outcomes in locally advanced esophageal/GEJ squamous cell cancer (SCC) is an unmet need. We investigated the addition of oral metronomic chemotherapy (OMC) following definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: This was a randomized open-label integrated phase II/III study in patients with SCC of esophagus/GEJ following definitive CRT who had no radiologic evidence of progression, and no endoscopically detected disease. Randomization was 1:1 to OMC (celecoxib 200 mg twice daily and methotrexate 15 mg/m2 weekly) for 12 months or observation. The primary endpoint for the phase II portion was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. P ≤ 0.2 for PFS was required to proceed to phase III. RESULTS: Between Jan 2016 and Dec 2019, we enrolled 151 patients for the phase II portion, 75 to OMC and 76 to observation. The tumor originated in the upper thoracic esophagus in 79% patients. Concurrent CRT consisted of median 63 Gy in a median of 35 fractions; concurrent chemotherapy was weekly paclitaxel + carboplatin in 91%. OMC was started at a median of 2.6 months (IQR 2.3-2.8) from CRT completion. Grade 3 or higher toxicities occurred in 18 patients (24%) in the OMC arm and 9 (12%) in the observation arm; P = 0.071. Median PFS was 25 months (95% CI, 17-58) in the OMC arm and was not attained [NA] (95% CI, 25-NA) in the observation arm; HR, 1.51, 95% CI, 1-2; P = 0.073. Median OS was 36 months (95% CI, 23-NA) in the OMC arm, and not attained (95% CI, NA-NA) in the observation arm; HR, 1.77; 95% CI, 1-2.9; P = 0.023. CONCLUSION: Oral metronomic methotrexate and celecoxib in patients who have not progressed radiologically and have no endoscopic evidence of disease following radical CRT for locally advanced esophageal/GEJ SCC does not improve outcomes and may lower survival. [Funded by the TMC-Research Administration Council (TRAC); CHROME study (CHemoRadiotherapy followed by Oral Metronomic therapy in Esophageal cancer); ctri.nic.in number: CTRI/2015/09/006204]. TRIAL REGISTRATION NUMBER: CTRI/2015/09/006204.

Cu(OAc)2/DABCO-mediated domino reaction of vinyl malononitriles with cyclic sulfamidate imines: access to 6-hydroxyaryl-2-aminonicotinonitriles.

A novel Cu(II)-salt/DABCO-mediated one-pot access to a myriad of highly substituted biologically relevant 2-aminonicotinonitriles possessing a resourceful phenolic moiety with satisfactory yields is reported. This method involves cyclic sulfamidate imines as 1C1N sources and different kinds of acyclic/cyclic vinyl malononitriles as 4C sources for pyridine synthesis via a vinylogous Mannich-cycloaromatization sequence process, creating two new C-N bonds under mild conditions. Importantly, this de novo strategy is applicable to gram-scale syntheses, underlining the method's practicability and allowing for a wide range of substrates with excellent functional group tolerance.

Repeat biopsy in epidermal growth factor receptor mutation-positive nonsmall cell lung cancer: Feasibility, limitations, and clinical utility in Indian patients.

INTRODUCTION: The feasibility and success rate of repeat biopsy for epidermal growth factor receptor (EGFR) mutation-positive lung cancers that have progressed on tyrosine kinase inhibitors (TKIs) are varied and merits further assessment. MATERIALS AND METHODS: EGFR mutation-positive lung cancers were offered repeat biopsy upon progression on TKIs. Two groups of patients, first one on a clinical trial and second one from a database, were included for analysis. The feasibility to perform a repeat biopsy was analyzed in the first group. Success rate of biopsy and tissue adequacy for molecular testing was analyzed in both groups. Descriptive statistics were used for analyzing the demography, EGFR mutation type, tissue adequacy, and molecular profile at repeat biopsy. Kolmogorov-Smirnov test was used to assess normality of data. Two sample t-tests were used for comparison of proportions. RESULTS: The feasibility of undergoing repeat biopsy was 77% (95% confidence interval [CI] of 69.4%-83.5%) in the first group (114/148 patients). Feasibility was not analyzed in the second group of patients. Out of 196 patients who underwent a repeat biopsy, 154 patients (78.6%; 95% CI: 72.2%-84.1%) had tumor tissue adequate for performing molecular testing. 27/196 (13.8%) patients did not have any evidence of malignancy on repeat biopsy whereas 15/196 (7.6%) patients had scanty tissue on repeat biopsy prohibiting molecular testing. Six patients (3.06%; 95% CI: 1.1%-6.5%) had small cell transformation. T790M mutation was detected in 12 out of the 42 patients (28.6%; 95% CI: 15.7-44.6) in whom EGFR testing was performed on repeat biopsy specimen. CONCLUSION: Repeat biopsy was able to provide adequate tissue acquisition in only two-thirds of the patients. Liquid biopsy represents an important tool to bridge this gap.

Response to docetaxel and cisplatin induction chemotherapy of locally advanced head and neck squamous cell carcinoma: a multicenter, non-comparative, open-label interventional pilot study.

BACKGROUND: Docetaxel, cisplatin plus 5-fluorouracil is an efficacious induction regimen but is more toxic than cisplatin plus 5-fluorouracil. This study aimed to determine whether docetaxel and cisplatin without 5-fluorouracil maintains efficacy while decreasing toxicity. METHODS: A multicenter non-comparative pilot study of locally advanced squamous cell carcinoma of the head and neck was performed. Patients received primary therapy comprising three cycles of 75 mg/m2 docetaxel and 75 mg/m2 cisplatin followed by concurrent chemoradiotherapy. The primary endpoint was the response rate to the docetaxel and cisplatin induction regimen. RESULTS: A total of 26 patients were enrolled: of these, 23 (88.5 per cent) received all three docetaxel and cisplatin cycles. Common grade 3-4 adverse events were febrile neutropenia (19.2 per cent of patients), diarrhoea (19.2 per cent) and non-neutropenic infection (15.4 per cent). The overall response rate to docetaxel and cisplatin induction chemotherapy was 65.4 per cent. A total of 23 patients (88.5 per cent) subsequently received chemoradiotherapy with a median radiotherapy dose of 70 Gy. The response rate to chemoradiotherapy was 73 per cent. At a median follow up of 44 months, the 3-year progression-free survival and overall survival rates were 62 per cent and 69 per cent, respectively. CONCLUSION: Docetaxel and cisplatin induction chemotherapy is a feasible induction regimen with comparable efficacy to docetaxel, cisplatin and 5-fluorouracil induction chemotherapy.

Ab initio and density functional theory studies on vibrational spectra of 3-hydroxy-3-(2-methyl-1H-indol-3-yl)indolin-2-one.

Computational studies have been carried out on 3-hydroxy-3-(2-methyl-1H-indol-3-yl) indolin-2-one (HMI) using both the DFT-B3LYP/6-311+G and HF/6-311+G methods. The optimized geometry of HMI and its bonding parameters as well as IR spectra have been calculated and analyzed. It can be seen that the calculated bond lengths are in good agreement with the reported bond lengths of indole and isatins. The calculated spectra have been compared with the available experimental FT-IR spectra. From vibrational frequency analysis, it can be seen that the vibrational frequencies obtained from B3LYP method are in good agreement with the experiment, when compared to HF method and there is an excellent correlation with the 0.999 regression coefficient between the experimental and calculated vibrations for HMI. The geometrical parameters, non-linear optical properties and thermodynamic properties are calculated and reported.

Are we eliminating cures with antibiotic abuse? A study among dentists.

CONTEXT: The theme of "World Health Day 2011" is "combat drug resistance- No action today, No cure tomorrow" which is very pertinent. The present study emphatically demonstrates the current issues related to the overwhelming concerns regarding indiscriminate use of antibiotics, leading to a bleak tomorrow where cures may be few. AIM: To know the prescription pattern of antibiotics for various dental procedures by dental practitioners. MATERIALS AND METHODS: A pretested questionnaire was used which contained two sections pertaining to prescription of antibiotics for healthy and medically compromised patients during various dental procedures, with therapeutic and prophylactic considerations. RESULTS: Questionnaire response rate of 66.6% was observed. Amoxicillin emerged as the most preferred antibiotic for dental procedures both as a therapeutic and a prophylactic drug. 50% of the endodontists and 40% of the general dentists opted to prescribe antibiotics during root canal therapy where ideally operative intervention would have sufficed. Overuse of antibiotics for routine scaling and extraction was observed. CONCLUSION: The dental profession as a whole needs to acquire a deeper understanding of the global effects of superfluous antibiotic prescription. Antibiotics when judiciously used are precise life-saving drugs.

Preliminary study to test the feasibility of using a local lymph node type of approach to characterize respiratory allergens.

There is a critical need to develop animal models that can characterize the potential of respiratory allergy. Dust-mite allergens are one of the major etiological agents in the induction of allergy and asthma in humans. In this study, the effects of intratracheal injection with dust-mite allergen were investigated by analyzing the in vivo proliferative response of lung-draining hilar lymph nodes and histopathological changes in the lung parenchyma. Balb/c mice were inoculated intratracheally with dust-mite allergens, a mixture of Dermatophagoides farinae and D. pteronyssinus dissolved in phosphate-buffered saline, or with an equal volume of saline alone. After 1 week, all the mice were injected intravenously with radioactive (3)H-thymidine and sacrificed 5 h later so as to assess the radioactivity incorporated into the hilar lymph nodes. The results indicated a marked increase in the proliferative response in the hilar lymph nodes of the animals treated with the dust-mite allergen as compared to the response of the control group. Treatment with dust-mite allergen also caused perivascular and interstitial eosinophilic inflammation of the lungs, hyperplasia of bronchus-associated lymphoid tissue, and an increase in the eosinophil peroxidase activity in the lungs. These results indicate that intratracheal injection with dust-mite allergen can trigger a number of changes consistent with respiratory allergy, including an increased proliferation in the draining lymph nodes.

Effects of sublethal radiation on bone marrow cells: induction of apoptosis and inhibition of antibody formation.

As part of the study to investigate the mechanism of radiation-induced immunosuppression, the survival and functional ability of bone marrow cells was analyzed by exposing C57B1/6 mice whole body to 2.0-Gy gamma-rays. There was a rapid induction of DNA fragmentation in the total bone marrow cells and the kinetics indicated that apoptosis reached a peak by 4 h and then dropped back to normal control levels within 10 h after irradiation. To determine the functional ability of bone marrow cells which survive the radiation treatment, animals were immunized with antigen trinitrophenyl (TNP)-lipopolysaccharide. There was a significant decrease of anti-TNP plaque-forming cells in the bone marrow of irradiated mice compared to control animals. Flow cytometric analysis of bone marrow revealed a significant depletion of both immature (B220+, Ig-) as well as mature (B220+, Ig+) B cells compared to control group. In summary, the present study showed that sublethal whole body irradiation inhibits antibody responses elicited by bone marrow cells. This decreased immune response may have been due to depletion of B lineage subsets as well as generalized apoptosis in the entire bone marrow cells.

Inhibition of natural killer cell activity in mice treated with tobacco specific carcinogen NNK.

Among the different chemicals present in tobacco and tobacco smoke, 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK) is the most potent carcinogen. In the present study the immunosuppressive effect of NNK was investigated in laboratory animals by analyzing the antitumor immune responses. Mice of B6C3F1 strain were treated with different doses of NNK by IP and assayed for natural killer cell activity by the lysis of 51Cr-labeled YAC-1 lymphoma cells. The control mice received physiological saline. The results showed a significant inhibition of natural killer cell activity in the spleen cells of mice treated with 100 or 250 mg/kg NNK. In contrast to the high-dose NNK group, treatment of mice with lower doses of NNK like 10 or 50 mg/kg had no significant effect on the natural killer cell activity. In addition to spleen, the natural killer cell activity was also suppressed in the hilar lymph nodes and lung cells of NNK-treated mice. The clearance of 125I labeled YAC-1 tumor cells was also reduced from the lungs of mice injected with NNK. Further, the metastatic potential of B16F10 melanoma cells was significantly higher, as evidenced by the increased lung tumor nodules in the high-dose NNK-treated mice. The decreased antitumor immune response in the carcinogen-treated mice was not due to a decrease of NK cells, because flow cytometric analysis indicated no change in the frequency of NK 1.1+ cells between control and treated animals. However, there was an increased plasma cortisone levels in the carcinogen-treated mice compared to control animals. Injection of mice with poly I:C or interleukin-12 was able to restore natural killer cell activity in the tobacco carcinogen-treated mice.

Immunologic alterations in bleomycin-treated mice: role of pulmonary fibrosis in the modulation of immune responses.

Among the side effects of bleomycin (BLM), a drug frequently used in the treatment of lymphomas and squamous-cell carcinomas, is pneumonitis with pulmonary fibrosis. The most prominent biochemical lesion associated with pulmonary fibrosis, a chronic debilitating and sometimes fatal disease, is an increase in the levels of collagen in the lung parenchyma. The mechanisms involved in the induction of this disease are still unclear, although results have suggested that the development of fibrosis may be immunologically mediated. There have, however, been no reports in the literature on the frequency and function of lymphocytes in the regional and systemic lymphoid tissues in BLM-induced pulmonary fibrosis. We therefore conducted a study, in which we inoculated C57Bl/6 mice intratracheally with BLM or saline, and tested the animals' lymphoid cells for various cell-mediated and humoral immune responses. The results indicated an increase in the number of lymphocytes in the lung-associated hilar lymph nodes, whereas the number of splenic lymphocytes was reduced as compared with control mice. Moreover, there was a significant inhibition of the antibody response to sheep erythrocytes in both the spleen and hilar lymph nodes of BLM-treated mice. Inhibition of the immune system appeared to be associated with the development of pulmonary fibrosis, and not to result from BLM toxicity, since the immune response of mice was not inhibited when they were injected with an identical dose of BLM under conditions that did not cause pulmonary fibrosis. Moreover, inhibition of splenic antibody responses was also observed in a hapten-induced model of pulmonary fibrosis, providing additional evidence that the induction of fibrosis and not the chemical toxicity of BLM was responsible for the modulation of immune responses.

Rapid communication: effect of irradiation on lymphocyte proliferation and differentiation: potential of IL-6 in augmenting antibody responses in cultures of murine spleen cells.

Ionizing radiation induces both quantitative and qualitative changes in the lymphoid cells of both man and experimental animals, including inhibition of antibody responses. However, the cellular basis of this immunological lesion is not clear. In the present study, groups of mice were exposed to 2.0 Gy gamma-rays or sham irradiated, and 2 days later animals were killed and spleen cells were cultured with TNP-Ficoll and assayed for antibody responses. Results indicated a significant decrease in the number of anti-TNP, plaque-forming cells in cultures from the irradiated mice compared with cultures from the control. When lymphocytes were stimulated in vitro with anti-IgM or anti-CD3, there was a decreased proliferation in spleen cell cultures derived from the irradiated mice compared with those from the control. Since radiation treatment was found to deplete both T and B cells in equal proportions in spleen and an equal number of both control or treated cells were used in culture, the immunological abnormalities may have been due to intrinsic defects in irradiated cells. Addition of IL-6 to irradiated spleen cell cultures was able to augment anti-TNP, plaque-forming cell responses indicating the possibility that in the future this cytokine can be used in vivo to induce protection from infectious diseases in irradiated individuals.

Immunostimulatory potential of smokeless tobacco extract in in vitro cultures of murine lymphoid tissues.

Despite numerous studies on the general toxicologic effects of smokeless tobacco (ST) little immunotoxicologic information is available. As a first step in assessing the potential activity of ST on the immune system, the effects of an aqueous extract of ST was studied in in vitro cultures of mouse lymphoid cells. There was a significant increase in the proliferation of spleen cells cultured with different concentrations of ST extract. The polyclonal IgM antibody responses as determined by protein A plaque assay were also elevated in ST stimulated spleen cell cultures. Similar immunostimulatory results were seen in the mesenteric lymph node cell cultures also. ST extract was able to stimulate the spleen cells of the immune defective CBA/N mice. The mitogenic ability of ST extract may not be due to lipopolysaccharide (LPS) contamination as determined by its response in the LPS resistant C3H/HeJ mice spleen cells. ST extract was mitogenic not only to B cells but also to T cells. However the magnitude of response was less in T cells than in B cells. The proliferation of T cells was not accompanied by secretion of IL-2 or expression of IL-2 receptors on T cells. However there was an increase of IL-1 activity in spleen cells cultured with ST extract. Finally, activation of B or T lymphocytes by ST did not result in the elevation of intracellular calcium levels. Since ST is consumed orally, the chronic immunostimulation by ST in oral mucosal lymphoid tissues may be associated with the increased incidence of gingivitis, leukoplakia and oral cancer seen in human ST users.

Priming of peripheral lymph node B cells with TNP-Ficoll: role of lymphokines in B cell differentiation.

We have previously shown that peripheral lymph node (PLN) B lymphocytes of adult DBA/2J mice failed to make an antibody response to type 2 antigen TNP-Ficoll, but exhibited a good antibody response to type 1 antigen TNP-Brucella abortus. In the present study we wanted to find out whether the unresponsiveness of PLN B cells to TNP-Ficoll is due to defects in the early activation and proliferation stage or in the final differentiation stage of B cells. Therefore, we have used a two-step protocol of in vivo immunization of mice with TNP-Ficoll and the subsequent in vitro challenge with TNP-Brucella abortus and studied the anti-TNP plaque-forming cell (PFC) responses. The results indicate a three- to sixfold increase of PFC responses in PLN cell cultures derived from TNP-Ficoll-primed animals compared to saline control mice. This increased antibody response was TNP-specific as 93% of the PFC's were inhibited by TNP-lysine. Limiting dilution experiments confirm that the increase in anti-TNP PFC response from the TNP-Ficoll-primed animals was indeed due to an increase in TNP-specific precursor B cells. Further, the addition of rIL-5 or rIL-6 induced anti-TNP PFC in the TNP-Ficoll-primed and in control PLN cell cultures in the presence of antigen. However, in primed PLN cells lymphokines alone were sufficient to restore anti-TNP PFC response. In conclusion, our results show that in PLN, the TNP-Ficoll can induce proliferation of hapten-specific B cells but not final differentiation. These primed PLN B cells mature into antibody-secreting cells upon stimulation with TNP-BA or lymphokines.

Effects of cigarette smoke on the antibody responses to thymic independent antigens from different lymphoid tissues of mice.

The influence of cigarette smoke on the humoral immune response of mice was investigated in lymphocytes derived from the spleen, bone marrow (BM) and mesenteric lymph nodes (MLN). Mice of the DBA/2J or C57BL/6 strain were exposed to cigarette smoke of a standard research cigarette, 2R1, twice a day, ten puffs each in morning and afternoon for 20, 40 or 60 weeks. At the end of the smoking period, animals were immunized intraperitoneally with the thymic independent antigens polyvinyl pyrrolidone (PVP) or trinitrophenyl (TNP)-Ficoll. The antibody responses were analyzed using sheep red blood cells coated with PVP or TNP, in a plaque forming cell (PFC) assay. The results indicate a statistically significant inhibition of the antibody response induced by PVP but not by TNP-Ficoll in splenic B cells of smoke exposed mice compared to sham controls. When tested in other lymphoid organs, there was higher anti-TNP PFC response from the BM and MLN cells of smoke exposed animals compared to sham controls.

Physiology of murine B lymphocytes. II. Life-spans of mitogen and thymus-independent antigen (type 2) reactive B lymphocytes from aged mice.

We showed earlier that life spans of murine B lymphocytes could be estimated by measuring the functional reactivities of normal B cells upon transfer into x-linked immunodeficient (xid) mice, which do not respond to anti-mouse IgM (anti-mu) antibodies and thymic-independent type-2 (TI-2) antigens. Here the same approach was adopted, to evaluate the life spans of B-lymphocytes from aged mice. Spleen cells from normal young and aged mice were transferred into young or aged xid recipients and the decay kinetics were followed by measuring the proliferative response to anti-mu and PFC response to TNP-Ficoll, a prototype TI-2 antigen. The results indicated that anti-mu reactive B cells of both young and aged mice decayed with similar non-linear kinetics. About 50% of the donor cells decayed in 8-10 days, whereas, the remaining decayed at a slower rate and it appeared that the median life-expectancy of this latter population could be at least 3 weeks. Essentially, there was no apparent difference in the decay kinetics of anti-mu reactive B cells of young and aged mice. Unlike anti-mu reactive cells, TNP-Ficoll reactive B cells showed 2-3-fold enhancement in the PFC response during the first 2 weeks, and persisted at least until 5 weeks post transfer. This result indicated that TNP-Ficoll reactive B cells are long-lived. Further, it was found that the turn over rate of TNP-Ficoll reactive B cells was also very similar in young and aged mice. The environment of the aged mice also did not appear to have any effect since the survival profiles of anti-mu reactive B cells were the same in young or aged xid recipients. Altogether, these results suggest that aging does not significantly alter the life spans of mature B lymphocytes.

Primary antibody responses to thymus-independent antigens in the lungs and hilar lymph nodes of mice.

B lymphocytes from the pulmonary lymphoid tissues were stimulated with a variety of thymus-independent (TI) antigens by intratracheal (i.t.) immunization. Immune responses in the lungs and hilar lymph nodes (HLN), which are part of the localized lymphoid tissue, as well as in the spleen, the systemic lymphoid organ, were studied. Thus, primary i.t. immunization of mice with the TI-1 antigen trinitrophenyl-lipopolysaccharide (TNP-LPS) elicited both antigen-specific and polyclonal plaque-forming cell responses from HLN, lung, and splenic B lymphocytes. These responses appeared as early as 3 days after immunization and declined by day 7. Similar immunization with another TI-1 antigen, TNP-Brucella abortus, resulted in anti-TNP responses in both pulmonary and systemic lymphoid tissues, although the kinetics of the antibody response were different than those to TNP-LPS. Interestingly an i.t. immunization with a TI-2 antigen, TNP-Ficoll, failed to induce an anti-TNP PFC response from HLN and lung B cells, although there was good antibody formation from splenic B cells. Antibody response to TNP-Ficoll was restored in pulmonary tissues when mice were immunized with TNP-Ficoll mixed with unconjugated B. abortus. In conclusion, our results indicate that TI-1 and TI-2 antigens differ in their ability to induce antibody responses in the pulmonary lymphoid tissues. The inability of TNP-Ficoll to elicit an antibody response in pulmonary lymphoid tissues has significance in the development of vaccines containing bacterial polysaccharides.

Antibody responses to thymic independent antigens in the peripheral and mesenteric lymph nodes of mice.

Differentiation of B lymphocytes from various peripheral lymph nodes (PLN) of mice was studied in the in vitro and in vivo conditions. Subcutaneous (SC) immunization in the foot pads with thymic independent (TI)-2 antigens such as polyvinyl pyrrolidone (PVP), R36A, and Trinitrophenyl (TNP)-Dextran failed to elicit plaque forming cell (PFC) responses from the draining popliteal and inguinal lymph nodes, whereas the splenic B cells of these animals exhibited good PFC response. Injection of unconjugated Brucella abortus (BA) along with TNP-Dextran was able to induce anti-TNP PFC formation from the draining lymph node B cells. However, PVP + BA or R36A + BA failed to stimulate such antigen specific B cell responses from the lymph nodes. Since TI antigens are metabolized slowly because of their long repeating subunits, we measured antibody responses up to 8 weeks after SC immunization with TNP-Ficoll and failed to observe any anti-TNP IgM PFC in the lymph nodes. TNP-Ficoll, in contrast to TI-1 antigen TNP-BA, did not induce IgG PFC response in the draining lymph node cells. In in vitro cultures, TNP-Ficoll induced the B cell differentiation from mesenteric lymph node (MLN) cells but not from the PLN cells. This activation of MLN B cells with TNP-Ficoll was limited to normal DBA/2J mice and was absent in the MLN cells of X-linked immune defective CBA/N mice. Finally, there was good antibody response from the inguinal and lumbar lymph node cells after an intraperitoneal immunization with TNP-BA but not with TNP-Ficoll.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiology of murine B lymphocytes. I. Life-spans of anti-mu and haptenated Ficoll (thymus-independent antigen)-reactive B cells.

We have evaluated the life-span of B lymphocytes by measuring the functional reactivity of normal B cells upon transfer into xid mice, which do not respond to anti-mu, fluoresceinated-Ficoll (FL-Ficoll) and 2,4,6-trinitrophenyl aminoethylcarbamylmethyl Ficoll (TNP-Ficoll). After 4 days of transfer only 30-40% of anti-mu-reactive cells decayed leaving behind 60-70% of B cells which appeared to decay slowly. Even 10 days after transfer approximately 40% of anti-mu-reactive B cells can be recovered from the recipients. This result demonstrates the existence of heterogeneity in the life-spans of anti-mu-reactive B lymphocytes and that a major population (60-70%) of B cells persists beyond 4 days. Interestingly, the short-lived B cell subpopulation was not detected when the decay of the antigen-specific B cells was studied. Thus, TNP-Ficoll and FL-Ficoll-reactive B cells were found to be long lived and such B cells did not decline at all, even 5 months after transfer into xid mice.