Acceptor site(s) for T cell-replacing factor (TRF) on B lymphocytes. I. TRF-substituting activity of anti-TRF acceptor site(s) antibody in the triggering of B cells.

Abstract

Abstract Antiserum raised in TRF-non-responder (DBA/2Ha × BALB/c)(DC)F, male mice against TRF-responder parental BALB/c B cells induced augmented primary IgM anti-heterologous erythrocyte antibody responses when i.v. injected in combination with suboptimal doses of antigen into TRF high-response animals. Although injection of the antiserum alone induces a small but significant polyclonal PFC response, the antiserum acts synergistically with antigen to produce enhanced antigen-specific PFC responses. BALB/c nu/nu mice were used to demonstrate the ability of DCF1 male anti-BALB/c-B cell antiserum to substitute for helper T cell activity in the induction of a primary anti-SRBC IgM PFC response. The T cell-replacing character of the antiserum was further substantiated by the striking augmentation in BALB/c mice of anti-DNP IgM PFC responses to DNP-D-GL (a potent B cell tolerogen) toward which no T cell activity occurs. Thus, the DCF1 male anti-BALB/c-B cell antiserum contains antibody that is capable of substituting for TRF activity. Moreover, the fact that the F(ab’)2 fragment of the antibody reacted selectively with B cells as analyzed by the FACS, and that the augmenting activity of the antibody was also effectively absorbed out by B cells but not by T cells, further implies that the reactivity of the antibody is B cell specific. Finally, in order to test whether the TRF acceptor site(s) detected by this antibody is identical to or closely associated with the Lyb-3 (and -5 and -7) molecules, the effect of the antiserum on primary anti-SRBC responses was examined in CBA/N mice and other control strains of mice, including DBA/2Ha. The fact that injection of CBA/ N mice with SRBC in combination with the antiserum produced a greater than 10-fold increase in anti-SRBC PFC, just as in BALB/c mice, indicated that enhancement of the anti-SRBC responses is clearly due to a specific reaction of this antibody with a component that is different from Lyb-3 (and -5 and -7), which is absent in CBA/N mice. In contrast to this, administration of the antiserum failed to augment the anti-SRBC PFC responses in DBA/ 2Ha mice, indicating that the augmenting effect is clearly due to a specific reaction with a component that is absent in DBA/2Ha mice. An alloantiserum containing anti-TRF acceptor site(s) antibody that has B cell-triggering activity may provide us with the experimental strategy necessary for characterization of the TRF acceptor site(s) on B cells and for analysis of the fine mechanism of B cell triggering that occurs via this site.