Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia

Abstract

approved these studies. From a cohort of 237 patients with clinical and laboratory features of B-CLL, 25 patients with expansions of CD5 + /CD19 + B cells expressing surface membrane IgG or IgA were chosen and analyzed. All of the patients with surface membrane IgM + cells were obtained randomly; some of the IgG + cases were provided by others because of their surface membrane phenotype and therefore were not randomly acquired. Some patients and the V gene Nonstandard abbreviations used: arsonate (Ars); B cell antigen receptor (BCR); B cell chronic lymphocytic leukemia (B-CLL); double-stranded DNA (dsDNA); framework region (FR); germinal center (GC); heavy chain third complementarity-determining region (HCDR3); light chain third complementarity-determining region (LCDR3); single-stranded DNA (ssDNA); web antibody modeling (WAM).

The effect of immunoglobulin VH gene mutation status and other prognostic factors on the incidence of major infections in patients with chronic lymphocytic leukemia

“…There is growing evidence that a significant proportion of patients with CLL who have unmutated IgV H genes have almost identical antigen receptors, suggesting that their malignant cells are selected by specific antigens. 33,34 It is possible that patients with these ''antigen-driven'' diseases have a reduced ability to develop immune responses against different bacterial or viral antigens. Alternatively, the IgV H mutation status simply may reflect the degree of disease aggressiveness and immune deficiency.…”

Molecular evidence for EBV and CMV persistence in a subset of patients with chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors

“…[15][16][17][18][19][20][21][22] Sequence data were analyzed using the ImMunoGeneTics database (http://imgt.cines.fr). 30,31 Sequences with a germline identity X98% were considered as unmutated, and those with an identity o98% were considered as mutated.…”

“…[8][9][10] A rise in IGHV4-34 Abs is also observed in the serum of otherwise healthy individuals in response to acute infections with herpesviruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) and in acute Mycoplasma pneumoniae infections. [10][11][12][13] The immunoglobulin gene repertoire expressed by chronic lymphocytic leukemia (CLL) malignant B cells is biased and notable for the existence of subsets with quasi-identical (stereotyped) B-cell receptors (BCRs), [14][15][16][17][18][19][20][21][22][23][24] implying the recognition of structurally similar epitopes, likely selecting the leukemic clones. However, the nature of the selecting antigens and their interactions with CLL progenitors or the malignant cells themselves remain shadowy.…”

LCK Is an Important Mediator of B-Cell Receptor Signaling in Chronic Lymphocytic Leukemia Cells

“…It is widely accepted that signals generated by engagement of the B-cell receptor (BCR) play an important role in the pathogenesis of CLL (3). This is because the structure of the BCR in CLL cells from different patients can show a very high degree of similarity, indicating that antigens of a similar nature drive development of the disease (4,5). Such similarity of BCR structure may be particularly important for CLL cases with progressive disease where the leukemic cells bear unmutated immunoglobulin heavy chain variable (IgHV) genes [unmutated-CLL (UM-CLL)].…”