H‐2‐unrestricted polyclonal maturation without replication of small B cells induced by antigen‐activated T cell help factors

Abstract Lines and clones of helper T cells, specific for either horse or sheep erythrocytes, when brought together with specific antigen and I region‐histocompatible macrophages, release factors which stimulate B cells to replicate and mature to Ig secretion (BRMF). BRMF act differently on activated B cells and on resting, small B cells. B cell blasts, activated by either lipopolysaccharide (LPS) or by lipoprotein, as well as “background” B cell blasts of normal spleen, are restimulated by BRMF to continued replication and maturation to Ig secretion. Between 10 and 50% of the activated B blasts from spleens of a variety of mouse strains, either I region‐compatible or not, are stimulated. BRMF, therefore, act as B cell mitogens, stimulating activated B blasts to rounds of division and maturation to Ig secretion in the absence of specific antigen, irrespective of the H‐2 haplotype of the B blasts. Resting, small B cells, on the other hand, are not stimulated to replication by the same preparations of BRMF, even in the presence of specific antigen. However, within one day, large, blast‐like cells appear in culture. These blast‐like cells do not incorporate thymidine, do not divide, but mature to secretion of IgM and IgG. Within 4 to 5 days of stimulation by BRMF, about one‐third of all splenic B cells develop in this way, and 10–20% of them secrete sufficient amounts of Ig to form hemolytic plaques. Furthermore, activation of small, resting splenic B cells is H‐2‐unrestricted and polyclonal. The nonreplicating blast‐like cells lose their capacity to replicate as they mature to Ig secretion. This capacity, on stimulation with either LPS or with antigen‐activated T cell help, is reduced by 90–93% to 99.7% within 1–2 days. This loss of capacity to replicate is discussed in view of models for tolerance induction which imply clonal elimination by terminal maturation.