Deletion of the C26 Methyl Substituent from the Bryostatin Analogue Merle†23 Has Negligible Impact on Its Biological Profile and Potency.

Important strides are being made in understanding the effects of structural features of bryostatin 1, a candidate therapeutic agent for cancer and dementia, in conferring its potency toward protein kinase C and the unique spectrum of biological responses that it induces. A critical pharmacophoric element in bryostatin 1 is the secondary hydroxy group at the C26 position, with a corresponding primary hydroxy group playing an analogous role in binding of phorbol esters to protein kinase C. Herein, we describe the synthesis of a bryostatin homologue in which the C26 hydroxy group is primary, as it is in the phorbol esters, and show that its biological activity is almost indistinguishable from that of the corresponding compound with a secondary hydroxy group.

B cell memory following infection and challenge of channel catfish with Ichthyophthirius multifiliis.

B cell responses in channel catfish to infection with the parasitic ciliate Ichthyophthirius multifiliis were followed for 3 years. High titers of serum IgM antibodies recognizing I. multifiliis immobilization antigens were present 5weeks after immunizing infection, but by 1 year titers were at low or undetectable levels. Two to three years after infection the numbers of antibody secreting cells recognizing immobilization antigens in skin and head kidney of immune fish had decreased to the level found in uninfected controls. Challenge of immune fish showed they remained immune and that the numbers of antibody secreting cells recognizing immobilization antigens increased in skin but not head kidney. This suggests that antigen-specific memory B cells persisted for 3 years after infection and upon challenge differentiated into antibody secreting cells that localized in skin. Our results suggest that humoral immunity in channel catfish is maintained through IgM(+) memory B cells.

Cutaneous antibody-secreting cells and B cells in a teleost fish.

Antibodies in cutaneous mucus and skin of teleosts play a critical role in the protective immune response against infection. We demonstrate by ELISPOT that antibody-secreting cells (ASC), which include LPS-inducible B cells (plasmablasts) and non-replicating plasma cells, reside in low numbers in the skin of channel catfish. Following immunization against the protozoan parasite Ichthyophthirius multifiliis, which infects skin and gills, the number of ASC in skin increased 20-fold, indicating that the number of ASC in skin is dynamic and increases in response to parasite infection. The number of ASC in skin remained elevated for at least 17 weeks after the last parasite exposure. Cutaneous ASC included I. multifiliis-specific ASC, which undoubtedly serve as the primary source of cutaneous antibodies that confer long-term humoral immunity against reinfection. Our demonstration that skin contains B cells and plasma cells suggests that it is an integral component of the teleost immune system.