Endotoxin lethality and tolerance in mice: analysis with the B-lymphocyte-defective CBA/N strain.

Immune-defective and immunologically normal F1 mice derived from the CBA/N strain were used to study the influence of anti-endotoxin antibody on the lethal effects of endotoxin. Immune-defective F1 male mice were unable to make specific responses to purified preparations of E. coli O111:B4 endotoxin, whereas their immunologically normal F1 female littermates made excellent responses. The ability to form antibody to lipopolysaccharide (LPS) in these F1 mice did not influence either their natural resistance to endotoxin challenge or the effects of pretreatment with sublethal amounts of endotoxin on subsequent challenge with higher normally lethal doses. Furthermore, transfer of sera with high titers of anti-LPS antibody to mice prior to challenge with LPS failed to protect. Thus, anti-LPS antibody does not appear to play a critical role in protection of immune-defective (CBA/N X DBA/2) F1 male mice to the lethal effects of endotoxin or to the protective effects of a single sublethal dose of endotoxin on subsequent endotoxin challenge.

The use of transfer factor in a patient with agammaglobulinemia.

We have studied a 9-year-old boy with agammaglobulinemia treated for the past 6 years with exogenous gamma-globulin who was noted to have an immunoglobulin (Ig)M level of 35 mg/100 ml and circulating B cells as determined by immunofluorescence. Of the circulating lymphocytes, 41% had alpha-immunoglobulin heavy chains, 3% gamma chains, and 3% mu chains. Synthesis of gamma heavy chain classes showing wide heterogeneity and alpha and mu chains of restricted mobility was demonstrated by radioimmunoelectrophoresis. Because of the patient's poor clinical response to exogenous gamma-globulin administration and the paradoxic presence of circulating B cells, with the capacity to synthesize immunoglobulins in vitro, we elected to begin a course of therapy with transfer factor. After the initial four doses of transfer factor (2 x 10(8) lymphocytes/dose) his serum IgG rose from 50 to 130 mg/100 ml, the same level which he had previously attained during continuous exogenous gamma-globulin therapy. His serum IgG has remained at this level for the past 12 months with trimonthly booster doses of transfer factor. The patient has not required any additional gamma-globulin therapy and he has remained clinically asymptomatic. Our studies in a patient with agammaglobulinemia have shown that transfer factor therapy may affect immunoglobulin synthesis. The concurrent discontinuation of exogenous gamma-globulin administration makes it difficult to attribute the changes to only one or another aspect of therapy. We await further reports of the effects of transfer factor in the therapy of patients with B cell disorders.

Formation of antibody in the newborn mouse: study of T-cell-independent antibody response.

The ontogeny of immune responsiveness, as assayed by antibody formation in vitro, of mouse spleen lymphocytes to thymus-independent antigens is reviewed. Responsiveness to trinitrophenyl (TNP)-lipopolysaccharide and TNP-Brucella abortus appear soon after birth and one to two weeks before TNP-Ficoll or capsular polysaccharide of Streptococcus pneumoniae (SSS-III) elicits significant antibody formation. This hierarchy of responsiveness to antigens is also apparent in the CBA/N mutant mouse strain, which has a bone marrow-derived (B-) cell maturation arrest and fails to respond to either TNP-ficoll or SSS-III. These findings are interpreted to suggest sequential maturation of different populations or lines of B-lymphocytes, each of which can respond to a defined class of thymus-independent antigens. The implication for vaccine use in humans is that a late-appearing subclass of B-cells may be required for adequate immune responses to polyaccharide antigens.