A NOVEL MOLECULAR-COMPLEX EXPRESSED ON IMMATURE B-CELLS - A POSSIBLE ROLE IN T-CELL-INDEPENDENT B-CELL DEVELOPMENT

To identify surface molecules that may play a role in regulating ileal Peyer's patch (PP) B cell growth, we generated monoclonal antibodies (mAbs) and then selected them for a unique reactivity with ileal PP B cells. Flow cytometric analysis identified a mAb (SIC4.8R) that labele d 97% of ileal and 50-60% of jejunal PP sIgM(+)B cells. SIC4.8R also l abeled a subpopulation of cortical thymocytes but few B or T cells in other lymphoid tissues, including bone marrow. Immunohistochemistry re vealed intense SIC4.8R staining of B cells in the cortex of ileal PP f ollicles. SIC4.8R also labeled bovine PP B cells, a murine pro-B cell line, and pre-B cells in human bone marrow. Protein chemistry revealed that a structurally similar molecular complex was expressed on sheep ileal PP B cells and thymocytes and murine pro-B cells. Addition of so luble SIC4.8R to cultured ileal PP B cells reduced apoptotic cell deat h, elevated proliferative responses, partially inhibited anti-Ig-induc ed cell death, and induced IL-4 responsiveness. in contrast, soluble S IC4.8R had an antiproliferative effect on a mouse pro-B cell line. Fin ally, SIC4.8R labeling declined following the stimulation of ileal PP B cells with CD40 ligand. In conclusion, the present investigation det ermined that SIC4.8R identified a novel molecular complex that is expr essed at several stages of T cell-independent B cell development in a variety of mammalian species. This observation confirmed that PP B cel ls are developmentally distinct from other B cell populations in sheep and suggested that the bone marrow may not be a site of B lymphopoies is in young lambs.