Requirement for three signals in B cell responses. II. Analysis of antigen- and Ia-restricted T helper cell-B cell interaction.
We have recently reported that resting B cells must receive at least three different signals in a T helper cell (TH)-dependent as well as in a lipopolysaccharide (LPS)-induced B cell response (3), i.e., a specific TH signal (that can be bypassed by LPS), a nonspecific TH signal (mediated by Ia or antigen-nonspecific B cell helper factor), and an antigen (hapten) signal. In a system using male (H-Y) antigen-specific cloned TH of C57BL/6 origin and male (or female) B cells, we now confirm and extend these findings by demonstrating that H-Y-specific TH must see both H-Y and Ia determinants on the B cells (and not only on macrophages) to provide the first specific TH signal required for a plaque-forming cell (PFC) response. This signal was interfered with by a monoclonal anti-I-Ab antibody at the B cell level, was not mediated by detectable soluble factors (in contrast to the nonspecific signal also provided by the TH), and could be bypassed by LPS, in which case anti-I-Ab antibody had no effect. However, although the H-Y-specific TH induced a polyclonal PFC response (B cell differentiation) in the apparent absence of an antigen seen by the B cells, significant clonal expansion of PFC precursors occurred only when the B cells also recognized an antigen (hapten).
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002448:Cell Adhesion; D002460:Cell Line; D002999:Clone Cells; D005260:Female; D006241:Haptens; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007962:Leukocytes / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013945:Thymoma / Q000276:immunology; D013953:Thymus Neoplasms / Q000276:immunology
D006241:Haptens; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides