INDUCTION OF IGA B-CELL DIFFERENTIATION OF BONE-MARROW-DERIVED B-CELLS BY PEYERS PATCH AUTOREACTIVE HELPER T-CELLS

The objective of this study was to demonstrate in vitro that bone marrow-derived pro/pre-B cells bearing mu mRNA can switch their Ig heavy-chain isotype to that of alpha mRNA-expressing B cells after contact with Peyer's patches-derived activated autoreactive CD4(+) T cells. Bone marrow-derived pro/pre-B cells and activated autoreactive Peyer's patch, mesenteric lymph node, or spleen CD4(+) T cells were co-cultured in the presence of recombinant (r) IL-2, rIL-7, and Con A for 3 days. The mixed cultured cells were isolated for preparation of total RNA. Dot/slot hybridization, using murine C mu (pu3741) and C alpha (P alpha J558) Ig heavy-chain cDNA probes, detected C mu and C alpha Ig heavy-chain mRNA transcripts. The magnitude of each mRNA expression was measured demsitometrically. In addition, the secreted class-specific Ig contents from the co-cultured supernatants were measured. The results indicate that activated autoreactive Peyer's patch and mesenteric lymph node CD4(+) T cells provide a specific Ig heavy-chain switch from mu to alpha (Peyer's patch CD4(+) T cells > mesenteric lymph node CD4(+) T cells) in bone marrow-derived pro/pre-B cells and also assist to develop IgA-secreting plasma cells. The alpha heavy-chain switch and IgA production do not occur in the presence of activated autoreactive spleen CD4(+) T cells. These results support the view that autoreactive gut Peyer's patch CD4(+) T cells, at least, regulate IgA B cell heavy-chain switching and terminal differentiation during gut mucosal B cell development.