A B cell receptor with two Igalpha cytoplasmic domains supports development of mature but anergic B cells.
B cell receptor (BCR) signaling is mediated through immunoglobulin (Ig)alpha and Igbeta a membrane-bound heterodimer. Igalpha and Igbeta are redundant in their ability to support early B cell development, but their roles in mature B cells have not been defined. To examine the function of Igalpha-Igbeta in mature B cells in vivo we exchanged the cytoplasmic domain of Igalpha for the cytoplasmic domain of Igbeta by gene targeting (Igbetac-->alphac mice). Igbetac-->alphac B cells had lower levels of surface IgM and higher levels of BCR internalization than wild-type B cells. The mutant B cells were able to complete all stages of development and were long lived, but failed to differentiate into B1a cells. In addition, Igbetac-->alphac B cells showed decreased proliferative and Ca2+ responses to BCR stimulation in vitro, and were anergic to T-independent and -dependent antigens in vivo.
Reichlin
Amy
A
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA.
Gazumyan
Anna
A
Nagaoka
Hitoshi
H
Kirsch
Kathrin H
KH
Kraus
Manfred
M
Rajewsky
Klaus
K
Nussenzweig
Michel C
MC
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D015139:Blotting, Southern; D015153:Blotting, Western; D001853:Bone Marrow / Q000276:immunology; D001973:Bromodeoxyuridine; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology / Q000502:physiology; D017635:Clonal Anergy / Q000276:immunology; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005822:Genetic Vectors; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D017434:Protein Structure, Tertiary / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000276:immunology
D017931:DNA Primers; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D001973:Bromodeoxyuridine; D002118:Calcium