Induction of IgA B cell differentiation of bone marrow-derived B cells by Peyer's 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.
Kihira
T
T
UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903, USA.
Kawanishi
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H
D000818:Animals; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003208:Concanavalin A / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D007070:Immunoglobulin A / Q000096:biosynthesis*; D017578:Immunoglobulin Class Switching; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D037102:Lectins / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008211:Lymphocyte Cooperation; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D018076:DNA, Complementary; D007070:Immunoglobulin A; D007376:Interleukin-2; D015851:Interleukin-7; D037102:Lectins; D011994:Recombinant Proteins; D003208:Concanavalin A