COOH terminus of membrane IgM is essential for an antigen-specific induction of some but not all early activation events in mature B cells.
Transfectants of mature B cell lines that bind phosphorylcholine were made in order to understand the role of the COOH terminus of the mu chain of membrane IgM (mIgM) in generation of antigen-specific signals. A chimeric receptor (I-A alpha tail) was constructed by replacing 40 amino acids from the mu COOH terminus with that of major histocompatibility complex class II I-A alpha chain. The effect of wild-type and chimeric tails were studied on representative immediate-early antigen-specific signals. The I-A alpha tail hybrid, but not the wild-type receptor, was defective in antigen-driven Ca2+ mobilization, although it could effectively endocytose ligand-receptor complexes. Signal(s) transduced through the wild-type receptor led to transient induction of selected immediate-early gene messages (Egr-1, c-fos, Jun) above basal levels. However, the signal(s) generated after crosslinking of the I-A alpha tail receptor either showed no effect (c-fos) or actually repressed basal level expression of Egr-1 and Jun. Thus, we have established that receptor-mediated endocytosis can be distinguished from other early events associated with B cell activation, based on their differential dependence upon the structural fidelity of the COOH-terminal sequence of mIgM.
Parikh
V S
VS
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Nakai
C
C
Yokota
S J
SJ
Bankert
R B
RB
Tucker
P W
PW
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004705:Endocytosis; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007075:Immunoglobulin M / Q000737:chemistry / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*
D000941:Antigens; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D002118:Calcium