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 antihapten response in mice

Publisher Website
Google Scholar
Abstract
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 1st 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.