Differential sensitivity of B lymphocyte populations to IgM receptor ligation is determined by local factors.
Ligation of surface IgM on B cells responding to lipopolysaccharide (LPS) suppresses terminal differentiation and high-rate Ig secretion with no effect on proliferation. As shown here, different B cell populations show characteristic mean values of ligand concentration required for 50% inhibition, with Gaussian distributions of sensitivity to IgM receptor ligation that reflect cellular heterogeneity of 'al-or-none' inhibitions in single cells. Differential sensitivity of B cell populations to IgM ligation seems to be locally determined by the cellular environment and unrelated to the 'maturity' of the responding cells. Thus, while long-lived peritoneal B cells are 3- to 5-fold more resistant than splenic B cells, there is no difference in sensitivity between short- and long-lived B cells in the spleen. Furthermore, while B cells in bone marrow and spleen differ in sensitivity by two orders of magnitude, B cells differentiated in vitro from bone marrow pre-B cells are as resistant as splenic B cells. Moreover, bone marrow cell culture supernatants restore a high level of sensitivity in such cell populations. Differential sensitivity to IgM receptor ligation is reproduced by multivalent nominal antigen, in cell populations that show identical dose-response inhibition curves to direct activation of protein kinase C by phorbol esters. We conclude that the level of sensitivity to IgM ligation is independent of the life span or maturity of the B cell, but differentially regulated in vivo by putative tissue factors.
Modigliani
Y
Y
Unité d'Immunobiologie, CNRS URA 1961, Institut Pasteur, Paris, France.
Demengeot
J
J
Vasconcellos
R
R
Andersson
J
J
Coutinho
A
A
Grandien
A
A
D000818:Animals; D000831:Animals, Newborn; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism*; D012680:Sensitivity and Specificity; D012995:Solubility; D013154:Spleen / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; C044203:anti-IgM; C035311:immunoglobulin M receptor; D013755:Tetradecanoylphorbol Acetate