Analysis of human V H gene repertoire expression in peripheral CD19+ B cells

Abstract

Using CD19 B-cell selection and polymerase chain reaction-amplified cDNA libraries, we analyzed the peripheral immunoglobulin heavy chain variable repertoire of three healthy adult donors. Here we report that most of the CD19+ circulating B cells expressed unmutated VH-D-JH rearrangements. By specific VH family hybridization, we show that VH gene family utilization in the periphery roughly corresponds to the complexity of these families in the germline and appears to be relatively constant among the analyzed subjects. However, sequence data of clones picked at random from one IgM cDNA library reveals that in spite of this "random" utilization, the VH gene expression in naive circulating B cells is highly biased towards the expression of a limited set of VH genes. As previously reported by others, this restricted mechanism is also found for the D and JH segments.

Selective Usage of VH Genes in Adult Human B Lymphocyte Repertoires

“…The VH gene utilization in adult individuals has been partly characterized [26][27][28][30][31][32]55], but the question of selection of B cells from the available to the actual repertoire has not been addressed. Our results show that the actual and available B cell repertoires display different patterns of VH gene family utilization.…”

“…The expression of human Ig VH genes has been characterized using PCR amplification of cDNA and in situ hybridization techniques in fetal and cord blood B cells [9,15,[23][24][25][26][27][28] and peripheral blood B cells from healthy adults [29][30][31]. While it has been confirmed that human fetal B cells express a restricted set of VH genes, predominantly members of VH clan III [15,24], the information on the Ig VH gene utilization in normal adults is contradictory.…”

Evidence of biased immunoglobulin variable gene usage in highly stable B-cell chronic lymphocytic leukemia

“…SPSS Table 1 References and other sources used for the construction of the IgV database [27][28][29][30][31][32] The complete nucleotide and aa sequence of V H 3-72 genes utilized by highly stable B-CLL are represented in Figure 1.…”

Molecular analysis of immunoglobulin variable genes in human immunodeficiency virus-related non-Hodgkin's lymphoma reveals implications for disease pathogenesis and histogenesis

“…Conversely, the pool of non-neoplastic, activated/memory B cells of HIV-positive patients displays reduced usage of the IGHV3 family. [36][37][38][39][40][41] In particular, the depletion of IGHV3 B cells is directly correlated to the reduction of the CD4 count and/or to viral load. 16,39,42 The reduction of IGHV3 B cells mainly involves the IGHV3-23 and IGHV3-30/3-30.5 genes that directly bind HIV gp120, and may be accompanied by an increase in the relative representation of IGHV4 B-cells.…”