Biochemical basis of synergy between antigen and T-helper (Th) cell-mediated activation of resting human B cells.
We have utilized CD23 expression as a marker for B cell activation in order to investigate the biochemical basis for synergy between antigen and T helper (Th) cells in the activation of resting human B cells. Our results confirm that while ligation of surface immunoglobulin (sIg) receptors by antigen analogues (e.g., F(ab')2 goat anti-human IgM) does not lead to CD23 expression, this stimulus markedly enhances CD23 expression induced during antigen specific Th-B cell interaction or by rIL-4. Utilizing a panel of monoclonal anti-human IgM antibodies, we observed a positive correlation between the capacity of a particular antibody to synergize with rIL-4 in CD23 expression and with B cell growth factor in B cell proliferation; suggesting that synergy in CD23 expression reflects the transduction of a functionally important signal via the sIg receptor. We next assayed analogues of the "second messenger" molecules, released during inositol lipid hydrolysis, for their capacity to amplify CD23 expression. These studies showed that protein kinase C (PKC) activating phorbol esters and the synthetic diacylgylcerol analogue, DiC8, synergize with either Th cells or rIL-4 in CD23 expression, while under no experimental condition does increasing B cell [Ca2+]i with ionomycin enhance CD23 expression. Taken together, these data suggest that activation of B cell PKC is the crucial biochemical event that primes antigen-activated B cells to respond more vigorously to interaction with Th cells and/or their soluble products.
Chartash
E K
EK
Department of Medicine, New York Hospital-Cornell University Medical College, New York 10021.
Crow
M K
MK
Friedman
S M
SM
D000911:Antibodies, Monoclonal / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D011493:Protein Kinase C / Q000378:metabolism; D011961:Receptors, Fc / Q000276:immunology*; D017455:Receptors, IgE; D011994:Recombinant Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D007140:Immunoglobulin Fab Fragments; D007075:Immunoglobulin M; D011961:Receptors, Fc; D017455:Receptors, IgE; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D015759:Ionomycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium