B cell defects in SLP65/BLNK-deficient mice can be partially corrected by the absence of CD22, an inhibitory coreceptor for BCR signaling.
CD22 is an inhibitory coreceptor for B cell receptor (BCR) signaling. The inhibition is most likely mediated by activation of SHP-1. We found that SLP65/BLNK reaches maximal tyrosine-phosphorylation at earlier time points in CD22(-/-) than in wild type B cells upon BCR cross-linking, suggesting that SLP65/BLNK is a substrate of SHP-1. However, in contrast to the defective Ca(2+) mobilization of SLP65/BLNK(-/-) B cells, there was a clear Ca(2+) response in SLP65/BLNKxCD22 double-deficient B cells. This implies that SLP65/BLNK is not the sole target of SHP-1 in the regulation of the Ca(2+) signaling strength. While SLP65(-/-) mice show several blocks of B cell differentiation, in SLP65/BLNK x CD22 double-deficient mice the maturation block of B cells in the spleen was partially rescued. However, the proliferative responses of B cells from both SLP65/BLNK(-/-) and double-deficient mice were defective after IgM- or CD40-stimulation. These results show that SLP65/BLNK is not absolutely essential for Ca(2+) induction in B cells, because the deficiency of this adapter can be by-passed by the additional deletion of an inhibitory receptor. Furthermore, these experiments suggest that B cell maturation in the spleen is directly dependent on the strength of BCR-derived Ca(2+) signals.
Gerlach
Judith
J
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
Ghosh
Snigdha
S
Jumaa
Hassan
H
Reth
Michael
M
Wienands
Jürgen
J
Chan
Andrew C
AC
Nitschke
Lars
L
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C113939:B cell linker protein; D002352:Carrier Proteins; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D014443:Tyrosine; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse; D002118:Calcium