ACCUMULATION OF SOMATIC HYPERMUTATION AND ANTIGEN-DRIVEN SELECTION INRAPIDLY CYCLING SURFACE IG(-CELLS WHICH OCCUPY GC AT A HIGH-FREQUENCYDURING THE PRIMARY ANTIHAPTEN RESPONSE IN MICE() GERMINAL CENTER (GC)B)

Well-developed germinal centers (GC) contain rapidly dividing surface immunoglobulin-negative (sIg(-)) B cells (centroblasts), and most of t heir progeny are sIg(+) B cells (centrocytes) in a resting state. It h as been predicted that somatic hypermutation occurs in centroblasts, w hereas antigen-driven selection takes place in centrocytes. The presen t analysis indicates that murine GC B cells bearing sIg with specifici ty for an immunizing antigen are in a rapidly cycling state and increa se exponentially in number to occupy spleen GC at high frequency durin g the Ist week after primary immunization; however, the number of thes e cells is significantly reduced in the 2nd week of immunization. Duri ng that period, these proliferating sIg(+) GC B cells accumulate somat ic hypermutations with nucleotide exchanges indicative of affinity mat uration. These sIg(+) GC B cells co-express B7-2, ICAM-1, and LFA-1, a nd have potent antigen-presenting activity which results in T cell act ivation in vitro. These observations indicate that the sIg(+) GC B cel ls accumulate somatic hypermutations and undergo antigen-driven select ion through proliferation, probably upon activation by T cells. This s Ig(+) GC B cell population may represent cell cycling centrocytes; how ever, the possibility that these may represent centroblasts undergoing re-expression of sIg could not be excluded.