Induction of IgA B Cell Differentiation of Bone Marrow-Derived B Cells by Peyer's Patch Autoreactive Helper T Cells

Abstract

The objective of this study was to demonstrate in vitro that bone marrow-derived pro/pre-B cells bearing μ mRNA can switch their Ig heavy-chain isotype to that of α 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 Cμ (pu3741) and Cα (Pα J558) Ig heavy-chain cDNA probes, detected Cμ and Cα 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 μ to α (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 α 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.

Key Words:

• Peyer's patch T cells
• gut mucosal IgA B cells
• differentiation of gut mucosal B cell)