Inducible cell contact signals regulate early activation gene expression during B-T lymphocyte collaboration.
B cells get help in the antibody response by presenting processed Ag to Th cells. We asked whether the Ag-presenting B cell must induce Th functions before receiving help, or whether B cell activation is a direct consequence of T cell recognition of Ag on the B cell surface. To obtain a prompt and sensitive indication of the receipt of growth signals, we measured mRNA levels of the immediate early genes, c-myc and egr-1, in T and B cells separated from Ag-specific B-T conjugates of normal, resting murine B cells and a Th line. Although Ag-dependent increases in B cell c-myc expression occur as early as 2 h after conjugation, early c-myc expression in the B cell was also seen when the Th cells were activated with immobilized anti-CD3 in the absence of Ag recognition. Therefore, T cell activation rather than Ag recognition per se appears to be responsible for the early c-myc signal in the B cells. The c-myc response in the B cell depends on induction of a contact-dependent helper function in the T cell, which is inhibitable by cyclosporin A acting on the T cell. Delivery of contact help is not blocked by anti-class II MHC antibody. Contact with activated Th cells induces a different pattern of immediate early gene expression from that induced by cross-linking the B cell Ag receptor.
Klaus
S J
SJ
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester 01655.
Parker
D C
DC
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology*; D017252:CD3 Complex; D002450:Cell Communication; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D015870:Gene Expression; D016259:Genes, myc; D017874:Immediate-Early Proteins; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*
D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D016572:Cyclosporine