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B-cell activation in vitro by helper T cells specific to a protein region that is recognized both by T cells and by antibodies.

This laboratory had previously mapped the regions of T and B cell recognition on sperm whale myoglobin (Mb). Mb has five regions (E1-E5) that are recognized by both T cells and B cells (i.e. antibodies, Abs) and an additional region (E6) that is recognized exclusively by T cells (i.e., TE6) and to which no Abs are detectable. The responses to the site are each under separate genetic control. Recently, we showed in an H-2d haplotype that TE6 cells preferentially activated Mb-primed B cells (BMb) that made Abs against sites within E3 and E4 on the same protein. In the present work, we established, from Mb-primed SJL mice, an E4-specific T cell line (TE4) by passage in vitro with synthetic peptide E4. At relatively low numbers, these T cells activated syngeneic BMb cells in vitro to produce anti-Mb Abs that recognized each of the antigenic sites within regions E1, E2, E3, E4 and E5. We confirmed the ability of TE4 to activate B cells that produce Abs against each of these regions by allowing TE4 to activate in vitro syngeneic B cells that had been primed with E1, E2, E3, E4 or E5. The helper activity of TE4 cells was dependent on the in vitro concentration of the challenge Ag (intact Mb or peptide E4). Thus, T cells against an epitope may provide help restricted to B cells that make Abs against selected antigenic sites or they may activate B cells that make Abs against all the antigenic sites of a protein. This might depend on the site-specificity of the T cell and/or on the host.