Factors that influence formation of B cell repertoire

V, D, and J gene segments rearrange at different frequencies in vivo. In my laboratory, we are interested in determining the reasons for this unequal rearrangement of V genes during B cell development, and also in gaining ins ights into the mechanisms that control recombination. Every V, D, and J gen e segment is flanked on its recombining side(s) by a recombination signal s equence (RSS), which is composed of a conserved heptamer and nonamer, separ ated by a spacer of conserved length. In this article, we summarize data sh owing that in many cases the RSS can account for differences in recombinati on frequencies observed in vivo. The approach that we use is to determine t he frequency of initial rearrangement of the V genes in vivo. The RSSs of t wo V genes are then placed into a competition recombination substrate to de termine the relative frequency with which the two RSS s recombine. In one e xample, we have shown that a single base pair polymorphism in the RSS of a V kappa gene may play a major role in susceptibility to Haemophilus influen zae type b infection.