Immature B cells from neonatal mice show a selective inability to up-regulate MHC class II expression in response to antigen receptor ligation.
Immature and mature B cells show phenotypic and functional differences. Thus immature B cells are functionally unresponsive to stimuli including ligation of slg and CD38 which induce proliferation in mature B cells. Furthermore, immature B cells have been widely shown to be hypersensitive to tolerance induction. To investigate the reasons for this differential responsiveness we have compared the ability of mature and immature B cells to show receptor-induced tyrosine phosphorylation of cellular substrates, a receptor-proximal response and MHC hyperexpression, which occurs later. Mature and neonatal B cells displayed a similar pattern of slg-induced tyrosine phosphorylation and their responses had similar kinetics. Importantly, cross-linking of slg on immature B cells induced tyrosine phosphorylation of substrates with mol. wt corresponding to the chains of the lg alpha beta dimer, which plays a critical role in B cell signalling. Immunofluorescence analysis showed that immature B cells constitutively express lower levels of MHC class II than their mature counterparts, consistent with previous studies. Here we report for the first time that immature B cells fail to hyperexpress class II after slg ligation, although this response is induced by other stimuli. These observations suggest that the ability to up-regulate class II is developmentally regulated in the B cell lineage. Moreover, the selective failure of slg-induced class II hyperexpression shown by immature B cells may not allow effective T-B cell collaboration and contribute to tolerance induction.
Tasker
L
L
Department of Human Anatomy and Cell Biology, University of Liverpool, UK.
Marshall-Clarke
S
S
D000818:Animals; D000831:Animals, Newborn; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; D017493:Leukocyte Common Antigens