The role of class II molecules in human B cell activation. Association with phosphatidyl inositol turnover, protein tyrosine phosphorylation, and proliferation.
Cross-linking class II molecules on resting human B cells can initiate phosphatidyl inositol turnover and an increase in intracellular calcium concentration levels comparable with that seen with the cross-linking of surface Ig receptors. The calcium response is most evident on dense B cell fractions: buoyant cells are less responsive, even though the levels of class II expression are similar on dense and buoyant tonsillar B cells. Human B cell lines exhibit the same absence of correlation between intensity of the calcium signal and levels of surface class II expression, indicating that responsiveness is related to the state of differentiation of the cell rather than the amount of class II expressed. Cross-linking class II on normal B cells or B cell lines caused accumulation of inositol phosphates, suggesting class II induces calcium release from intracellular stores, rather than through direct regulation of calcium channels. The calcium response mediated through class II was completely abolished by bringing the protein tyrosine phosphatase, CD45, into close proximity with surface class II. This result indicated that protein tyrosine phosphorylation might regulate the signal transduced through this molecule. In support of this notion we found that tyrosine phosphorylation is induced when small dense tonsillar B cells are stimulated with either anti-Ig or with antibodies to class II. Finally, in B cell proliferation assays we show that cross-linking class II molecules on dense tonsillar B cells synergize strongly with suboptimal concentrations of PMA or IL-4. The significance of these results is discussed with regard to the cognate signal between B and T lymphocytes.
Regional Primate Research Center, University of Washington, Seattle 98195.
P J
PJ
Lane
F M
FM
McConnell
G L
GL
Schieven
E A
EA
Clark
J A
JA
Ledbetter
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000502:physiology; D002455:Cell Division; D003432:Cross-Linking Reagents; D004306:Dose-Response Relationship, Immunologic; D006681:HLA-D Antigens / Q000502:physiology*; D006649:Histocompatibility Antigens / Q000502:physiology; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D014066:Palatine Tonsil / Q000166:cytology; D010716:Phosphatidylinositols / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism*; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D003432:Cross-Linking Reagents; D006681:HLA-D Antigens; D006649:Histocompatibility Antigens; D007148:Immunoglobulin mu-Chains; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium