CEACAM1 is a potent regulator of B cell receptor complex-induced activation.
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, CD66a) is a member of the immunoglobulin (Ig) superfamily, previously characterized as an adhesion and signaling molecule in epithelial, endothelial, and hematopoietic cells. Here, we show that the CEACAM1 isoform expression pattern is different in nonactivated and activated primary mouse B lymphocytes and that CEACAM1 influences B cell receptor complex-mediated activation. A CEACAM1-specific monoclonal antibody strongly triggered proliferation of mouse B cells when combined with surface IgM cross-linking. However, anti-CEACAM1 was not mitogenic when added alone. The proliferation was more pronounced and lasted longer as compared with other activators of B cells, such as anti-IgM in the presence of interleukin-4 or lipopolysaccharide. A similar, costimulatory effect was exerted by CEACAM1-expressing fibroblasts, indicating that homophilic CEACAM1-CEACAM1 cell-mediated binding is the physiological stimulus for CEACAM1-triggered B cell signaling. The anti-CEACAM1/anti-IgM-activated cells aggregated in a lymphocyte function-associated antigen-1-dependent manner. Furthermore, cells that were activated by anti-CEACAM1/anti-IgM secreted Ig but did not go through Ig class-switching. Anti-CEACAM1 induced phosphorylation of c-Jun N-terminal kinase (stress-activated protein kinase) but did not activate the extracellular signal-regulated kinase or p38 mitogen-activated protein kinases.
Greicius
Gediminas
G
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden.
Severinson
Eva
E
Beauchemin
Nicole
N
Obrink
Björn
B
Singer
Bernhard B
BB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000378:metabolism; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D005347:Fibroblasts; D006023:Glycoproteins / Q000276:immunology / Q000502:physiology*; D007075:Immunoglobulin M; D048031:JNK Mitogen-Activated Protein Kinases; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D007075:Immunoglobulin M; D016169:Lymphocyte Function-Associated Antigen-1; D011947:Receptors, Antigen, B-Cell; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases