The CD5/CD72 receptor system is coexpressed with several functionally relevant counterstructures on human B cells and delivers a critical signaling activity.

Abstract

The CD5 molecule is expressed on T cells and, at a lower density, on a minor B cell subset (CD5+ B cells). The pan-B Ag CD72 was recently identified as the CD5 counterstructure, and several data suggest the involvement of this ligand pair in T-B cell cognate interaction. However, the functional role of CD5 and CD72 molecules within the B cell compartment is still unknown. In this work we studied umbilical cord blood CD5+ B cells (B-1a), adult splenic CD5- B cells (B-2), and CD5+ B cells from patients with chronic lymphocytic leukemia. Flow cytometry analysis and proliferation assays were used to determine 1) the ability of B-1a and B-2 cells to coexpress functionally relevant counterligands other than CD5 and CD72, and 2) the signaling capacity of CD5 and CD72 in terms of B cell activation and proliferation. To this purpose, freshly isolated or preactivated normal and neoplastic B cells were cultured with agonistic anti-CD5 or anti-CD72 mAbs in the presence or the absence of cytokines equipped with B cell activity. Our data demonstrate that CD5 and CD72 molecules are coexpressed with other ligand pairs usually involved in T-B cell cognate interaction on B-1a cells, but not on B-2 cells. CD5 and/or CD72 engagement delivers critical costimulatory signals in B-1a, B-2, and B cells from patients with chronic lymphocytic leukemia, but with different requirements and patterns. Besides suggesting the potential involvement of B-1a lymphocytes in B-B cell interactions during T-independent B cell responses, our results indicate that CD5 and CD72 counterstructures play a functional role in the B cell compartment.

CD5 provides viability signals to B cells from a subset of B-CLL patients by a mechanism that involves PKC

“…Then, it seems that the differences in culture time and mAb concentration could explain the discrepancy between our results and those of Pers et al and Cioca and Kitano. On the other hand, our findings are in agreement with a previous study in which is described that CD5 is capable of transducing positive signals [26]. In this work, Cerutti et al showed that CD5 engagement delivers critical costimulatory signals in B-CLL B cells, as well as in B-1a and B-2 lymphocytes, although with different requirements and patterns.…”

“…Probably, reflecting the clinical heterogeneity observed in patients, several signalling pathways may become affected during the initiation and course of this lymphoproliferative disorder. According to this, B-CLL cells have shown heterogeneous responses to stimulation via cell surface receptor including CD40 [53], BCR [40,[54][55][56][57] and CD5 [28,26,27]. Here, we have demonstrated that CD5-signalling pathway is also heterogeneous but, in contrast with previously published data, we found that this pathway can induce viability in some patients.…”

“…Since previously published data suggested that CD5 triggering could enhance the proliferation of B-CLL B cells [26], we next checked if the extended survival observed in some samples was due to proliferation. Cell proliferation in response to anti-CD5 was quantified by BrdU incorporation and staining with a FITC-conjugated anti-BrdU antibody.…”

“…It has been shown that stimulation with anti-CD5 mAbs in B-1 and B-CLL B cells increase IL-2 secretion [26], cytokine that may be involved in the regulation of viability in an autocrine fashion [48]. Regarding this, we proposed to analyse the possible implication of IL-2 in CD5-mediated survival in B-CLL patients.…”

“…Also, activation of protein kinase C-ζ (PKC-ζ) through diacylglycerol (DAG) and members of the MAPK cascade seem to be downstream events of the CD5 signalling pathway [25]. In B-CLL there are few studies to date which have addressed the possible role of CD5 molecule in activation or proliferation processes, the activation of A-SMase has been shown to occur after CD5 cross-linking [25], as well as the induction of IL-2 and a discrete proliferation of leukaemic B cells [26]. In contrast, the majority of works have reported CD5-induced apoptosis in these lymphoproliferative disease [27][28][29].…”