CD5 does not regulate the signaling triggered through BCR in B cells from a subset of B-CLL patients

Abstract

CD5 is a transmembrane protein expressed on all T lineage cells and a subset of B cells. It is known that CD5 is physically associated with the T-cell receptor and B-cell receptor (BCR), inhibiting the signaling triggered by both of them. CD5 is also characteristic of B-chronic lymphocytic leukemia (B-CLL) B cells, although its implication in the development of this lymphoproliferative disorder has not been studied. In the present study, we examined the effect of CD5 in apoptosis, cell viability and global protein tyrosine phosphorylation mediated by BCR in B cells from B-CLL patients. As opposed to tonsil B cells, we did not observe an increase in the apoptotic or viability signals induced by anti-immunoglobulin M or SAC/interleukin-2 when CD5 was dissociated from BCR in leukemic cells of the majority of patients. We also observed that CD5 did not regulate the BCR-induced phosphotyrosine pattern in B-CLL B cells. These findings suggest that CD5 does not inhibit properly the BCR-mediated signaling in leukemic cells. This defect in inhibiting the BCR might contribute to the enhanced survival of B-CLL B cells.

Immunological aspects in chronic lymphocytic leukemia (CLL) development

“…CD5 protects from autoimmunity by several mechanisms that include the inhibition of BCR early signaling events [34], maintains tolerance in anergic B cells [28], and induces the secretion of IL-10 in B cells [29]. Unfortunately, in some cases CD5 does not properly inhibit BCR-mediated signaling in CLL B cells [71]. Disturbances in CD5+ function have been detected in subsets of patients with CLL.…”

“…Disturbances in CD5+ function have been detected in subsets of patients with CLL. Significantly, CD5 does not regulate the signaling triggered through BCR in B cells from a subset of B-CLL patients [71], provides viability signals to B-CLL cells [72, 73], promotes IL-10 secretion in CLL-B cells [74], and protects from apoptosis [75]. …”

“…CD5 expression protects B lymphocytes from uncontrolled self-reactivity by increasing the BCR signaling threshold; however, CD5 does not properly inhibit BCR-mediated signaling in CLL B cells [72]. In addition, CD5+ can also promote the autocrine production of IL-10 [71, 72]. Interestingly, these mechanisms could promote the release of regulatory IL-10 [111], thereby fostering the generation of B cells [69], with the subsequent capacity to induce an infectious tolerance and block T cell immune responses [112].…”

“…Notably, CD5 provides viability signals and leads to IL-10 production, which acts as an autocrine growth factor for leukemic B cells [72]. However, CD5 does not properly inhibit BCR-mediated signaling in CLL B cells [71]. It is possible that autoantigen stimulation through BCR in an autoreactive B cell guide the expression of CD5+ by increasing the threshold for BCR activation to avoid the process leading to antibody production.…”

Prognostic significance of aberrant CD5 expression in B-cell leukemia

“…and the signaling pathways triggered by CD5 marker itself. 4,12,13 Phosphorylation and activation of STAT3 via B-cell linker protein (BLNK) and CK2 complex is a well-known signaling pathway. Following the phosphorylation of STAT3, this factor goes into the nucleus and turns on the target genes.…”