Differential effects of the stimulation of complement receptors CR1 (CD35) and CR2 (CD21) on cell proliferation and intracellular Ca2+ mobilization of chronic lymphocytic leukemia B cells.
The regulatory role of CR1 and CR2 on B cell activation and proliferation has been investigated by using B cells from patients with chronic lymphocytic leukemia. The chronic lymphocytic leukemia B cells are clonal expansions of B lymphocytes frozen at specific stages of activation. They displayed two patterns of response upon surface Ig (sIg) cross-linking in terms of in vitro proliferation and intracellular free Ca2+ mobilization: cells from patient F (first pattern) proliferated in the presence of mitogenic anti-mu antibodies, whereas cells from patient A (second pattern) did not respond to sIg cross-linking but proliferated in the presence of low m.w. B cell growth factor and IL-2. Coculture of A or F cells with C3b-bearing SRBC led to a two- to four-fold increase in thymidine incorporation in cultures containing low m.w. B cell growth factor but not in cultures containing rIL-2. This enhanced proliferation was inhibited by F(ab')2 polyclonal rabbit antihuman CR1 antibodies. Only cells which proliferated in the presence of anti-mu (cells F) responded to cross-linking of sIg with a rise in intracellular Ca2+. No increase in calcium mobilization was observed after co-cross-linking of CR1 and sIg on A and F cells with mAb or polyclonal anti-CR1 antibodies. Co-cross-linking of CR2 with sIg only led to an enhanced intracellular Ca2+ rise in F cells but not in A cells. The lack of CR2-mediated synergy in Ca2+ rise in A cells indicates that the synergy occurs only if there is a proper coupling of sIg to phospholipase C. CR1-induced proliferation of B cells does not involve the signaling pathways of sIg. These results provide additional evidences for the role of C3 fragments in modulation of human B cell activation.
Hivroz
C
C
INSERUM U 108, Hôpital Saint-Louis, Paris, France.
Fischer
E
E
Kazatchkine
M D
MD
Grillot-Courvalin
C
C
D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D010716:Phosphatidylinositols / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011951:Receptors, Complement / Q000096:biosynthesis / Q000502:physiology*; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D007075:Immunoglobulin M; D010716:Phosphatidylinositols; D011947:Receptors, Antigen, B-Cell; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D015847:Interleukin-4; D002118:Calcium