B cell antigen receptor-mediated apoptosis. Importance of accessory molecules CD19 and CD22, and of surface IgM cross-linking.
Engagement of the B cell Ag receptor can induce a suicide pathway in various B cell types. Earlier studies showed that anti-IgM mAb treatment triggers apoptotic death in the Burkitt lymphoma-derived cell line, Ramos. We show that two B cell surface molecules, CD19 and CD22, which have been reported to interact either functionally or structurally with the B cell Ag receptor, also stimulate cell suicide when sufficiently aggregated, both in the Ramos and EBV-infected Ramos AW cell lines. In conditions of lower cross-linking, both molecules enhance the apoptotic response induced by a suboptimal dose of anti-IgM mAb in Ramos cells, reinforcing the notion that CD19 and CD22 may be involved in the death pathway and modulate Ag-induced B cell apoptosis. Similar outcomes were obtained with human tonsillar B cells, which enter the death program upon treatment with cross-linked anti-IgM, -CD19, or -CD22 mAbs. These results indicate that Ag-induced B cell suicide may affect mature B cells in the periphery and may be regulated via the interaction of CD19 and/or CD22 with their respective ligand(s). Early tyrosine phosphorylations were analyzed by Western blotting. The biologic outcome of these various treatments--cell survival or death--could not be related to any detectable new tyrosine-phosphorylated substrate, further questioning the biochemical basis of apoptosis signaling.
Chaouchi
N
N
INSERM U131, Clamart, France.
Vazquez
A
A
Galanaud
P
P
Leprince
C
C
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D015153:Blotting, Western; D015815:Cell Adhesion Molecules; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology* / Q000378:metabolism; D037102:Lectins; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D007075:Immunoglobulin M; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2