PERITONEAL-CAVITY CD5 (BLA) B-CELLS - CYTOKINE-INDUCED IGA SECRETION AND HOMING TO INTESTINAL LAMINA PROPRIA IN SCID MICE

The mouse peritoneal cavity contains a unique population of B cells (Bla) with a high IgM/low IgD ratio, CD5(+) (Ly1), MAC-1 + phenotype. These cells arise early in ontogeny, utilize a limited repertoire of immunoglobulin V genes, produce polyreactive IgM antibodies and have been implicated as the source of many auto-reactive immunoglobulins. Recent data from chimeric mice suggest that this B cell population also contains the precursors of many IgA plasma cells found in the lamina propria of the small intestine. In the present study we have investigated the potential of this cell population to secrete IgA (and IgG) in response to various cytokines. IL-5 alone, or in combination with IL-2, greatly enhanced secretion of both IgG and IgA. Cytokine-induced IgA secretion resulted from expansion of a subset of CD5 B cells co-expressing sIgA. Adoptive transfer of CD5 B cells to severe combined immunodeficient (SCID) mice resulted in repopulation of lamina propria with sIgA(+) B cells while peripheral lymph nodes contained only IgM(+) and some IgG(+) B cells. Transfer of CD5(+) B cells also reconstituted serum IgM, IgG and IgA levels in recipient SCID mice. These studies demonstrate that CD5(+) B cells have the potential to secrete IgA and IgG, immunoglobulins characteristic of mucosal and anamnestic responses, when cultured in vitro with the appropriate cytokines. These cells also give rise to IgA plasma cells in the intestinal lamina propria following adoptive transfer to SCID mice, further supporting the hypothesis that cells of this lineage may be important in immune responses at mucosal surfaces.