Accumulation of somatic hypermutation and antigen-driven selection in rapidly cycling surface Ig(+) germinal center (GC) B cells which occupy GC at a high frequency during the primary anti-hapten response in mice

Well-developed germinal centers (GC) contain rapidly dividing surface immunoglobulin-negative (sIg(-)) B cells (centroblasts), and most of their progeny are sIg(+) B cells (centrocytes) in a resting state. It has been predicted that somatic hypermutation occurs in centroblasts, whereas antigen-driven selection takes place in centrocytes. The present analysis indicates that murine GC B cells bearing sIg with specificity for an immunizing antigen are in a rapidly cycling state and increase exponentially in number to occupy spleen GC at high frequency during the Ist week after primary immunization; however, the number of these cells is significantly reduced in the 2nd week of immunization. During that period, these proliferating sIg(+) GC B cells accumulate somatic hypermutations with nucleotide exchanges indicative of affinity maturation. These sIg(+) GC B cells co-express B7-2, ICAM-1, and LFA-1, and have potent antigen-presenting activity which results in T cell activation in vitro. These observations indicate that the sIg(+) GC B cells accumulate somatic hypermutations and undergo antigen-driven selection through proliferation, probably upon activation by T cells. This sIg(+) GC B cell population may represent cell cycling centrocytes; however, the possibility that these may represent centroblasts undergoing re-expression of sIg could not be excluded.