Production of autoantibodies by CD5-expressing B lymphocytes from patients with chronic lymphocytic leukemia.

Abstract

Based primarily on studies in the mouse, it has been postulated that at least two separate lineages of B cells exist (reviewed in reference 1). The first lineage, characterized by the cell surface expression of the Ly-1 antigen, appears to be primarily responsible for the secretion of antibodies that display extensive autoreactivity. The second lineage, characterized by the lack of Ly-1 expression, is primarily responsible for the production of "conventional", non-self-reactive antibodies (2-5). This distinction has been most convincingly demonstrated in inbred strains of mice with a genetic predisposition for the development of various autoimmune syndromes (6, 7).The human counterpart ofthe Ly-1 antigen, recently termed CD5, was originally defined using the anti-Leu-1 mAb (8). In this (8) and subsequent (9-12) studies, it was demonstrated that the expanded monoclonal population of B cells that develops in patients with chronic lymphocytic leukemia (CLL)' expresses the CD5 molecule. Thus, CLL appears to represent a clonal overexpansion of the putative autoantibody-producing B lymphocyte . In support ofthis notion are the clinical observations that the sera of patients with CLL occasionally contain autoantibodies and that -20% of such patients develop autoimmune phenomena such as hemolytic anemia (13).On the basis of these findings, the following prospective studies were performed to determine, at the clonal level, if the C135-expressing B cells in patients with CLL and other CD5' B lymphoproliferative disorders secrete mAbs reactive with autoantigens . These in vitro studies demonstrate that leukemic cells from >50% of patients with overexpansions of CD5' cells synthesize and can be made to secrete Ig that is autoreactive . Considering that these secreted mAbs were screened for reactivity with only a limited panel of autoantigens, it is conceivable that an even higher

Constitutive activation of the MAPkinase p38 is critical for MMP-9 production and survival of B-CLL cells on bone marrow stromal cells

“…This might also be the case for B-CLL cells, but the matter of fact that p38 MAPK maintained phosphorylated over 24 h during in vitro culture rather requires different pathomechanism(s): (I) A cell 'extrinsic' mechanism that causes a permanent interaction between a cell surface-receptor and ligand: Schattner et al have proposed that the interaction between CD40 and CD154, which are both expressed on a subset of malignant B cells, can contribute to a stage of activation and activate NF-kB in particular. The interaction between BCR, which often binds autologous structures, 31 and host antigens has also to be considered to permanently activate B-CLL cells. Certainly, this does not explain the long-lasting activation of p38 MAPK during in vitro culture.…”

Lymphoproliferation in primary sjögren's syndrome. evidence of selective expansion of a b cell subset characterized by the expression of cross‐reactive idiotypes

“…The same families of V, and V, genes are frequently used in a proportion of patients with essential mixed cryoglobulinemia, Waldenstrom's macroglobulinemia, and CLL (26,(33)(34)(35)(36)(37). The leukemic cells in CLL express the CD5 molecule and produce autoantibodies; the same subpopulation of B cells is found in increased numbers in peripheral blood and salivary gland samples from patients with primary SS (38-40).…”

The miR-17∼92 family regulates the response to Toll-like receptor 9 triggering of CLL cells with unmutated IGHV genes

“…In fact, UM BCRs are known to operate as polyreactive receptors that bind to various foreign and self antigens, although often with low affinity. 2,3 Besides antigen stimulation, the development and progression of CLL could also be affected by other external signals, synergistically cooperating to regulate the proliferation and survival of the malignant clone. In this regard, UM CLL cells have been recently found to respond more efficiently to microenvironmental pro-survival signals than mutated (M) CLL cells, being on the other hand more susceptible to spontaneous apoptosis when these signals are absent.…”