Cognate T cell help for CD40-deficient B cells induces c-myc RNA expression, but DNA synthesis requires an additional signal through surface Ig.
To investigate the role of CD40 ligand in the delivery of help to B cells, we examined the Ag-specific interaction of B cells from CD40-deficient mice with a Th2 cell line in vitro. Small resting B cells from normal mice are stimulated to synthesize DNA when they present monovalent Ag (rabbit Fab anti-Ig) to a rabbit Ig-specific Th cell line. This response, which is independent of a signal through the B cell Ag receptor (sIg), is nearly absent in B cells from CD40-deficient mice. The CD40-deficient B cells are not defective in Ag presentation because they induce T cell IL-4 synthesis as well as normal B cells. Also, CD40-deficient B cells respond to T cell help with DNA synthesis almost as well as normal B cells if an additional signal is provided through sIg. In conjunction with a sIg signal, cell contact with helper T cells induces DNA synthesis more effectively than soluble cytokines. CD40-independent T cell help can also be measured as an early increase in c-myc mRNA levels in CD40-deficient B cells presenting Ag to helper T cells, although the levels of c-myc RNA expression are lower than those in normal B cells. However, c-myc RNA induced by noncognate interaction with anti-CD3-activated T cells is completely CD40 dependent. We conclude that early growth signals from activated Th cells are received by CD40-/- B cells, but that CD40 and/or sIg signals are required for efficient induction of DNA synthesis.
Schrader
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CE
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester 01655, USA.
Stavnezer
J
J
Kikutani
H
H
Parker
D C
DC
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000032:analysis* / Q000235:genetics*; D003433:Crosses, Genetic; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D016259:Genes, myc / Q000187:drug effects / Q000235:genetics*; D008213:Lymphocyte Activation / Q000276:immunology; D008211:Lymphocyte Cooperation; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000494:pharmacology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D019013:CD40 Antigens; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell