Germline diversity of the expressed BALB/c VhJ558 gene family

Although the mouse immunoglobulin heavy chain (Igh) locus contains 15 heavy chain V (Vh) gene families, at least half of the Vh gene segments are memb ers of the VhJ558 family. This large Vh gene family represents the least ch aracterized germline coding regions of any of the mouse antigen receptor lo ci and the contribution of individual VhJ558 genes to the preimmune reperto ire is poorly understood. In fact, relatively few germline VhJ558 sequences have been reported for BALB/c, the foundation strain for mouse immunoglobu lin genetics and the prototypic strain of the Igh(a) haplotype. Here we pre sent a database consisting of 66 sequences estimated to represent one-half of the total number of functional BALB/c VhJ558 genes. Our results indicate that a subset of the VhJ558 genes is highly expressed in the preimmune rep ertoire, with just nine Vh sequences accounting for nearly 50% of the VhJ55 8 heavy chains expressed by splenic B cells. We show that this disparity in the expressed Vh gene repertoire is not due to the position of the Vh gene s relative to the Dh cluster or to multiple germline copies of the highly e xpressed VhJ558 genes. Together, these data constitute the first detailed a nalysis of functional BALB/c VhJ558 genes, demonstrate a striking bias in t he use of particular VhJ558 genes in the preimmune repertoire, and provide sufficient information to study the regulation of the Dh-distal region of t he Igh-V locus at the level of individual genes. (C) 2001 Published by Else vier Science Ltd.