Two classes of bystander B cell response: activation requirements reflect those of B cells in general.

Bystander anti-sheep red blood cell (SRBC) antibody responses were induced in cultures containing unprimed B cells, SRBC, particulate or soluble eliciting antigen, and helper T (Th) cells primed to the eliciting antigen. The use of long-term cultured Th cells, depleted of alloreactive cells, allowed direct assessment of the requirements for major histocompatibility complex- (MHC) restricted interactions in the cellular events leading to bystander B cell activation. H-2 restricted Th cell activation limited all bystander B cell responses; however, the requirement for H-2 restricted Th-B cell interactions varied with the state of activation of the responding B cell population before assay. Thus, we defined two classes of bystander B cell response. Activation of small (i.e., resting) SRBC-specific bystander B cells, purified by density gradient centrifugation, was completely restricted by B cell MHC. The requirement for high concentrations of eliciting antigen suggests that nonspecific binding of soluble or particulate antigen to the responding B cell surface plays a mandatory role leading to the activation of resting bystander B cells. The concomitant requirement for a restricted Th-B cell interaction suggests that this role is one of focusing antigen-specific, H-2 restricted T cell help to the resting B cell. In contrast, bystander responses, unrestricted by B cell MHC, were generated exclusively from large (i.e., blasted) B cells limited only by Th cell activation. This class of SRBC-specific bystander response correlated with an SRBC-dependent increase in the number of cells secreting antibodies that recognized degraded mouse RBC. Thus, we propose that the H-2 unrestricted anti-SRBC response is derived from the amplification of B cells activated in vivo to degraded homologous RBC. Both classes of anti-SRBC response were enhanced by the presence of the bystander antigen. This phenomenom is discussed in terms of a mitotic advantage provided by the interaction of antigen with surface immunoglobulin on specific bystander B cells.