Soluble anti-mu monoclonal antibodies prime resting B cells to secrete immunoglobulins in response to interleukins-4 and -5.
Soluble anti-immunoglobulin (Ig) antibodies have been generally found to inhibit Ig secretion in B cells, via largely unknown mechanisms. To investigate this phenomenon further a two-step culture system was used in which B cells are primed for 24-72 h with various soluble monoclonal or polyclonal anti-Ig antibodies: after washing the cells were placed in readout cultures with a combination of interleukin (IL)-5 and IL-4. Using this protocol B cells primed with (mitogenic or nonmitogenic) anti-mu monoclonal antibodies differentiated into large numbers of IgM-secreting cells, comparable to responses to lipopolysaccharide. In contrast, priming with polyclonal rabbit anti-Ig or monoclonal anti-kappa antibodies, markedly inhibited Ig secretion induced by IL-4 + IL-5. In addition, anti-mu was markedly inhibitory if left in the readout cultures with the two lymphokines. These results, therefore, indicate that appropriate cross-linking of surface IgM receptors on B cells can prime the cells to secrete Ig when they are restimulated by T cell-derived lymphokines in the absence of anti-mu. In contrast co-ligation of both surface IgM and surface IgD receptors apparently results in powerful inhibition of Ig secretion, which is not reversed by stimulation with IL-4 plus IL-5.
Phillips
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Laboratory of Cellular Immunology, National Institute for Medical Research, Mill Hill, London, Great Britain.
Klaus
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GG
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D007140:Immunoglobulin Fab Fragments; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D015847:Interleukin-4 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D015848:Interleukin-5; D015847:Interleukin-4