Role of the human CD38 molecule in B cell activation and proliferation

Abstract

Human CD38 is a surface molecule which has been attributed the function of a signaling channel leading to cellular activation and proliferation, an ectoenzyme with multiple function as well as an inducer of Ca2+ mobilization from cytoplasmic stores. The effect mediated by CD38 have been studied in different cell populations: the results obtained in human B cells are apparently contradictory, with CD38 simultaneously leading to apoptosis in early B cells while increasing survival in cells derived from lymph node germinal center. Other effects recently reported concern a different potential in terms of signaling in early B cells and derived cell lines or in more detailed disease models of human leukemia, namely B chronic lymphocytic leukemia cells. To complete the picture of the effects mediated by CD38 in the B cell compartment, we have studied the signals elicited by ligation of the human molecule in mature B cells from circulating pool and also from spleen of normal individuals. The information obtained completes the picture of CD38 and mature B cells, where we also studied the contribution of relevant cytokines involved in maintenance and differentiation of these normal cells, namely IL-1 alpha, IL-2, IL-4 and IL-6. Our results indicate that human CD38 plays a key role as a co-receptor in mature B cells from normal individuals.

Interferon-γ Promotes Antibody-mediated Fratricide of Acute Myeloid Leukemia Cells

“…Although CD38 is known for its pro-survival signaling (40,41), higher levels of CD38 could also make it more targetable by therapeutic antibodies, such as daratumumab. Indeed, certain agents are already being investigated for their ability to modulate CD38 expression for this purpose.…”

The metamorphosis of a molecule: from soluble enzyme to the leukocyte receptor CD38

“…Splenic B cells proliferate in response to IB4 mAb [39]. Addition of anti-CD38 mAbs (either IB4 or T16) to normal bone marrow B cells (Ͼ90% CD38 ϩ ) co-cultured on stromal layers (mostly CD38 Ϫ but CD157 ϩ ) drastically reduces the number of cells recovered after a 7-day culture period [9].…”

“…Biochemical attempts to answer this question by co-precipitation and crosslinking experiments have failed so far [20] but co-capping and co-modulation experiments have been successful. In T cells, CD38 co-localizes with the TCR/CD3 and down-modulation of CD38 also leads to the disappearance of the TCR/CD3 [33,35]. In B lymphocytes, CD38 has this same kind of liaison with CD19 and the B cell receptor (BCR) complex [38,43], and with CD16 (low affinity Fc␥RIII receptor) in NK cells [20].…”

“…Incubation of peripheral blood T cells or the T cell line Jurkat with IB4 mAb triggers signaling pathways that lead to (1) activation and proliferation [33], (2) transcription of cytokine genes [34], (3) increased intracellular calcium levels, (4) down-modulation of the TCR/CD3 complex, (5) up-regulation of CD5, CD28, CD69, and CD95, and (6) cell death by apoptosis [35].…”

Determinación fenotípica de subpoblaciones de células madre derivadas de sangre de cordón umbilical.

“…Otro de los marcadores que se expresa en los progenitores hematopoyéticos comprometidos es la molécula CD38, una glicoproteína expresada por muchos tipos celulares y que desempeña un papel importante en los procesos de activación y proliferación en los linfocitos maduros, además de estar involucrada en los procesos de interacción entre las células (6,7).…”