Germinal centers without T cells

Germinal centers are critical for affinity maturation of antibody (Ab) resp onses. This process allows the production of high-efficiency neutralizing A b that protects against virus infection and bacterial exotoxins. In germina l centers, responding B cells selectively mutate the genes that encode thei r receptors for antigen. This process can change Ab affinity and specificit y. The mutated cells that produce high-affinity Ab are selected to become A b-forming or memory B cells, whereas cells that have lost affinity or acqui red autoreactivity are eliminated. Normally, T cells are critical for germi nal center formation and subsequent B cell selection. Both processes involv e engagement of CD40 on B cells by T cells. This report describes how high- affinity B cells can be induced to form large germinal centers in response to (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll in the absence of T cells o r signaling through CD40 or CD28. This requires extensive cross-linking of the B cell receptors, and a frequency of antigen-specific B cells of at lea st 1 in 1,000. These germinal centers abort dramatically at the time when m utated high-affinity B cells are normally selected by T cells. Thus, there is a fail-safe mechanism against autoreactivity, even in the event of thymu s-independent germinal center formation.