Involvement of CD44 exon v10 in B‐cell activation

Abstract

The family of CD44 glycoproteins has been suggested to be involved in lymphocyte homing, maturation and activation. Using in vitro blocking studies with a monoclonal antibody, we here addressed the question of functional activity of CD44 variant exon v10 (CD44v10) in B-cell activation. We became interested in this question by the observation that CD44v10O was transiently expressed on activated T cells, B cells and monocytes as well as on a subpopulation of bone marrow cells. A potential ligand, as revealed by staining with a CD44v10 receptor globulin, was only detected on monocytes. Anti-CD44v10 had no major impact on T-cell activation and no influence on primed B cells, but interfered with the mounting of a primary B-cell response to T-independent and T-dependent antigens. Addition of anti-CD44v10 at different stages during the activation process revealed that CD44v10 was not engaged in B-cell-T-cell interactions. The antibody exerted some effect on monocyte activation as defined by a slight decrease in IL-1 production, but most efficiently inhibited antigen-specific as well as mitogen-induced B-cell activation when present during the coculture of virgin B cells with monocytes. These findings, together with the observation that a CD44v10 ligand was only detected on monocytes but not on lymphocytes, point towards a requirement for CD44v10 in a B-cell-monocyte interaction. Furthermore, since activation of B cells by engagement both of the B-cell receptor and of mitogen receptors was inhibited by anti-CD44v10, the data suggest that a costimulatory function of CD44v10 proceeds independent of the B-cell receptor.

CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells

“…Furthermore, transplanted HSC maturation towards T and B cells was more severely impaired in EL4 than EL4-v10 TB and was strongly affected by IM7. Instead, K926 only affected B cell maturation, which is in line with our earlier report on CD44v10 expression in B progenitor cells [30]. In vitro cocultures confirmed that EL4 more efficiently than EL4-v10 competed with HSC for BM-Str adhesion.…”

“…In addition, fewer HSC were recovered from late EL4 than EL4-v10 TB (Figure 2C). In late EL4-v10 TB a minor retention of Gr1 + cells in the BM and a slight reduction in serum IgG was noted (Figure 2C and D), which is in line with CD44v10 being engaged in monocyte and B cell maturation [30]. Reduced recovery of HSC in IM7-treated late TB could be in line with IM7, distinct to K926, interfering with HSC embedding in the osteogenic niche.…”

“…We choose the CD44v10 cDNA transfected thymoma EL4 (EL4-v10). CD44v10 is expressed on subpopulations of macrophages (Mϕ), activated Th1 cells and hematopoietic progenitor cells, particularly of the B cell lineage [30-34]. Upregulated CD44v10 expression correlates with Hodgkin’s disease relapse [34] and in multiple myeloma it supports adhesion to marrow endothelial cells [35].…”

CD44 supports T cell proliferation and apoptosis by apposition of protein kinases

“…Interestingly, the costimulatory effect was only observed with IM-7, but not with the anti-CD44 antibody KM81, which occupies the hyaluronic acid binding site of CD44. Cross-linking of CD44v10, which is weakly expressed on SC [27], was ineffective ( Fig. 2A).…”

CD44v10, osteopontin and lymphoma growth retardation by a CD44v10‐specific antibody

“…Side effects should be minimized, as CD44v expression is far more restricted, with few exceptions, and interacts only weakly in non‐transformed cells. It is also weakly expressed on subpopulations of macrophages (Mφ), activated Th1 cells and B progenitor cells 34 , 35 , 36 , 37 but more highly expressed on keratinocytes 38 . In some organ‐specific autoimmune diseases, CD44v10 is expressed in memory T helper (Th) and dendritic cells and contributes to progression by recruiting Th and supporting Th longevity, 34 which can be blocked by anti‐CD44v10 39 , 40 , 41 .…”