Expression of CD5 and CD38 by human CD5⁻ B cells: Requirement for special stimuli

Abstract

In this study the mode of expression of CD5 by human tonsillar CD5- B cells after stimulation with different agents was investigated. Resting B cells were separated into CD5+ and CD5- cells and the two cell fractions exposed to phorbol 12-myristate 13-acetate (PMA). CD5- B cells expressed CD5 and maximum CD5 expression was achieved after approximately 60 h of culture. Based upon the proportions of cells that express CD5 as well as those of the cells surviving in culture, it was calculated that 15-25% of the total CD5- B cells were induced to express CD5. Unlike CD5- B cells, CD5+ B cells proliferated vigorously in response to PMA as assessed by [3H]thymidine incorporation and cell cycle analysis in vitro. However, the expression of CD5 by CD5- B cells was not related to the selective expansion of some CD5+ B cells left over as contaminant cells since this occurred in the absence of cell proliferation. Upon exposure to PMA, CD5- B cells remained in the G0-G1 phases of the cell cycle and did not express the Ki67 antigen or incorporate [3H]thymidine. Furthermore, mitomycin C treatment of the CD5- B cells did not prevent CD5 expression. Phenotypic studies disclosed that CD5+ B cells but not CD5- B cells expressed CD39. This finding offered the opportunity to carry out an additional control experiment. Separation of the two populations according to the expression of CD39 confirmed the finding obtained by fractionating the cells into CD5+ and CD5- B cells. The cells induced to express CD5 also expressed CD38 that was not detected on resting CD5- B cells. In this respect, the CD5- B cells that converted into CD5+ cells (inducible CD5+ B cells) resembled the cells from the CD5+ B cell fractions that up-regulated CD5 and also expressed CD38 upon exposure to PMA alone. Another example of coordinate expression of these two antigens was the finding that exposure to PMA in the presence of recombinant interleukin-4 (rIL-4) resulted in inhibition of the expression of CD5 and CD38. Although virtually all of the tonsillar CD5- B cells expressed the CD69 activation marker, no cells other than those co-expressing CD5 and CD38 were induced to express CD5 by PMA alone. Resting CD5- B cells failed to express CD5 and/or CD38 when cultured with PMA in the presence of EL4 T cells and IL-4-free T cell supernatants.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of B-cell antigen receptor-associated molecules and lipid rafts in CD5-induced apoptosis of B CLL cells

“…A high expression level of CD38 characterized those patients sensitive to CD5 crosslinking. This confirms the involvement of CD38 in BCRtriggered apoptosis, 12,16 the behavior of CD38 and CD5 as inducible activation markers, 17 and the relationship between CD38 expression and early signaling through sIgM (Table 2). 16 However, while the combined stimulation of B-CLL cells with anti-CD38 mAb and IL-2 has been shown to prolong survival, 18 CD5 crosslinking favors apoptosis.…”

Intraclonal Complexity in Chronic Lymphocytic Leukemia: Fractions Enriched in Recently Born/Divided and Older/Quiescent Cells

“…By screening a panel of chemokine receptors expressed on clones from a series of CLL patients (4), we found an inverse relationship between CXCR4 and CD5 densities, with differing shapes among patients ( Figures 1A-D We reasoned that high CD5 density would reflect cellular activation as in normal human B cells (7), and low CXCR4 levels would identify cells that internalized the receptor because of an activation event and thereby passaged from a lymphoid tissue to the periphery (8). As detailed elsewhere (5), incorporation of 2 H into cellular DNA in patients given 2 H 2 O is a direct measure of newly synthesized DNA and hence cell division, thereby allowing study of birth rates of CLL cells in vivo (6,9,10).…”

ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile

“…It is intriguing that 5 of 7 of the ZAP-70 outliers were also discordant for CD38 expression. In addition to being a differentiation marker, CD38 surface expression can be induced by a variety of stimuli, including phorbol esters, 44 interferons, 45 and retinoic acid. 46 CD38 surface expression can vary over time in the same patient with CLL and, in some patients, increased CD38 expression can be associated with disease progression.…”