Conventional light chains inhibit the autonomous signaling capacity of the B cell receptor.
Signals from the B cell antigen receptor (BCR), consisting of mu heavy chain (muHC) and conventional light chain (LC), and its precursor the pre-BCR, consisting of muHC and surrogate light chain (SLC), via the adaptor protein SLP-65 regulate the development and function of B cells. Here, we compare the effect of SLC and conventional LC expression on receptor-induced Ca(2+) flux in B cells expressing an inducible form of SLP-65. We found that SLC expression strongly enhanced an autonomous ability of muHC to induce Ca(2+) flux irrespective of additional receptor crosslinking. In contrast, LC expression reduced this autonomous muHC ability and resulted in antigen-dependent Ca(2+) flux. These data indicate that autonomous ligand-independent signaling can be induced by receptor forms other than the pre-BCR. In addition, our data suggest that conventional LCs play an important role in the inhibition of autonomous receptor signaling, thereby allowing further B cell differentiation.
Meixlsperger
Sonja
S
Institute for Biology III, Albert-Ludwigs University of Freiburg and Max Planck Institute for Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany.
Köhler
Fabian
F
Wossning
Thomas
T
Reppel
Michael
M
Müschen
Markus
M
Jumaa
Hassan
H
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D054444:Immunoglobulin Light Chains, Surrogate; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D008024:Ligands; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D002118:Calcium