IgG1 B cell receptor signaling is inhibited by CD22 and promotes the development of B cells whose survival is less dependent on Ig alpha/beta.
We describe a mouse strain in which B cell development relies either on the expression of membrane-bound immunoglobulin (Ig) gamma1 or mu heavy chains. Progenitor cells expressing gamma1 chains from the beginning generate a peripheral B cell compartment of normal size with all subsets, but a partial block is seen at the pro- to pre-B cell transition. Accordingly, gamma1-driven B cell development is disfavored in competition with developing B cells expressing a wild-type (WT) IgH locus. However, the mutant B cells display a long half-life and accumulate in the mature B cell compartment, and even though partial truncation of the Ig alpha cytoplasmic tail compromises their development, it does not affect their maintenance, as it does in WT cells. IgG1-expressing B cells showed an enhanced Ca(2+) response upon B cell receptor cross-linking, which was not due to a lack of inhibition by CD22. The enhanced Ca(2+) response was also observed in mature B cells that had been switched from IgM to IgG1 expression in vivo. Collectively, these results suggest that the gamma1 chain can exert a unique signaling function that can partially replace that of the Ig alpha/beta heterodimer in B cell maintenance and may contribute to memory B cell physiology.
Waisman
Ari
A
Institute for Genetics, University of Cologne, 50674 Cologne, Germany.
Kraus
Manfred
M
Seagal
Jane
J
Ghosh
Snigdha
S
Melamed
Doron
D
Song
Jian
J
Sasaki
Yoshiteru
Y
Classen
Sabine
S
Lutz
Claudia
C
Brombacher
Frank
F
Nitschke
Lars
L
Rajewsky
Klaus
K
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D051925:CD79 Antigens / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D019281:Dimerization; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
D051925:CD79 Antigens; D007074:Immunoglobulin G; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D051193:Toll-Like Receptors; D002118:Calcium