Recruitment of virgin B cells into an immune response is restricted to activation outside lymphoid follicles

Abstract

The site and mechanism of recruitment of short-lived new B cells from the bone marrow into the longer-lived recirculating B-cell pool were studied by using kappa-allotype-distinct congenic rats to construct bone marrow chimeras. Chimeras were immunized with antigen in the form of an antigen-antibody complex that is largely restricted to lymphoid follicles, rapidly localizing to follicular dendritic cells (FDC). This form of antigen, although a potent stimulator of memory B cells, was shown to be a very poor inducer of virgin B-cell responses. This was not due solely to differences in receptor affinity, as complexes in which the hapten epitopes were unmasked also evoked little virgin B-cell response. The inability of virgin B cells to be activated by FDC-bound antigen seems to relate to the fact that they are not part of the recirculating pool and do not migrate through lymphoid follicles; restriction of antigen to a draining lymph node also precluded virgin B-cell activation. The evidence presented suggests that activation of virgin B cells at extrafollicular sites in the spleen (red pulp, marginal zone, outer periarteriolar lymphocytic sheath) is required for both their incorporation into immune responses and into the recirculating pool. These experiments also show that established immune responses are maintained by clones activated soon after immunization and not by continued incorporation of new clones.