Cognate T cell help for CD40-deficient B cells induces c-myc RNA expression, but DNA synthesis requires an additional signal through surface Ig
Department of Molecular Genetics and Microbiology
Animals; Antigen-Presenting Cells; Antigens, CD40; B-Lymphocytes; Crosses, Genetic; DNA Replication; Female; Gene Expression Regulation; Genes, myc; Lymphocyte Activation; *Lymphocyte Cooperation; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mice, Mutant Strains; Proto-Oncogene Proteins c-myc; RNA, Messenger; Receptors, Antigen, B-Cell; Signal Transduction; T-Lymphocytes
Life Sciences | Medicine and Health Sciences | Women's Studies
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.
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Citation: J Immunol. 1997 Jan 1;158(1):153-62.