Abnormal transcription factor induction through the surface immunoglobulin M receptor of B-1 lymphocytes.
Populations of murine peritoneal B-1 and splenic B-2 cells, highly purified by negative selection techniques, were used to demonstrate that B-1 cells completely fail to enter cell cycle in response to surface immunoglobulin M (sIgM) crosslinking without any decrease in cell number or viability. This failure of B-1 cell responsiveness appears to represent a specific defect in sIgM-derived signaling inasmuch as stimulation to enter S phase occurs normally in response to activated and fixed T cells, and to lipopolysaccharide (LPS). The level at which sIgM signaling fails was determined by evaluating the nuclear expression of the transcription factor complex, NF-kappa B, whose sIgM-mediated induction in B-2 cells is dependent on protein kinase C (PKC) activation but is independent of protein synthesis. There was no induction of nuclear NF-kappa B in B-1 cells stimulated by sIgM crosslinking, although NF-kappa B was stimulated by phorbol myristate acetate and by LPS. In contrast, NF-kappa B was induced in B-2 cells by all three stimuli. Thus, in B-1 cells, the sIgM-mediated induction of a transcription factor that is substantially stimulated by anti-IgM in B-2 cells is blocked. However, all sIgM-derived signaling in B-1 cells was not impaired inasmuch as anti-IgM increased I-A antigen expression. These results strongly suggest that sIgM receptor-mediated signaling in B-1 cells is interrupted early in the signal transduction pathway, at a point proximal to the activation of PKC. These results further demonstrate that transcription factor induction can be used to analyze the level at which receptor-mediated signaling is blocked.
Morris
D L
DL
Department of Medicine, Boston University Medical Center, Massachusetts 02118.
Rothstein
T L
TL
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004789:Enzyme Activation; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007075:Immunoglobulin M / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D010537:Peritoneum / Q000166:cytology; D011493:Protein Kinase C / Q000502:physiology; D011961:Receptors, Fc / Q000032:analysis / Q000502:physiology*; D016196:S Phase; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011961:Receptors, Fc; C035311:immunoglobulin M receptor; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate