Expression of the immunoglobulin VH gene 51p1 is proportional to its germline gene copy number.

Abstract

51p1 is an immunoglobulin VH gene that is frequently expressed in B cell chronic lymphocytic leukemia and early in B cell ontogeny. The 51p1 gene locus is highly polymorphic, consisting of 13 alleles that can be classified as being either 51p1-related or hy1263-related, based on distinctive sequence motifs in the second complementarity determining region. Two of the 51p1-related genes usually occur as a linked pair on the same haopltype, resulting from gene duplication. Consequently, a person can have a total of zero to four copies of 51p1-related genes. These genes are detectable in genomic DNA by sequence-specific RFLP analysis using oligonucleotide probes. Ig encoded by nonmutated 51p1-related genes can be detected by G6, a murine antiidiotypic mAb. We have now studied lymphocytes from 35 human tonsils to examine the relation between the number of 51p1-related germlime gene copies and the proportion of IgD-bearing tonsillar B cells that react with G6. All subjects who had zero copies of 51p1-related genes lacked any G6-reactive B cells, whereas those with four copies of 51p1-related genes had the highest proportions of G6-positive IgD B cells, up to 11.4%. Subjects with intermediate gene doses had intermediate proportions of G6-reactive B cells. Over the entire data set, the percentage of IgD-bearing B cells that reacted with G6 was proportional to the 51p1-related gene copy number (r = 0.92, p < 0.001), with each copy accounting for 2.4-4.0% of the IgD-bearing B cells. We conclude that 51p1-related genes are expressed by a relatively large percentage of IgD+ tonsillar B cells and this percentage is proportional to the germline copy number of 51p1-related genes.