LAT links the pre-BCR to calcium signaling.
SLP-65(-/-) mice display a partial block at the pre-B cell stage of development. Here, we show that LAT is required for the differentiation of SLP-65(-/-) pre-B cells. We show that LAT and SLP-76 are recruited to the pre-BCR and associated with Ig-alpha upon pre-BCR engagement, whereas LAT interaction with SLP-76 is already detected in untreated pre-B cells. Reconstitution of LAT or SLP-65 expression in SLP-65/LAT(-/-) pre-B cells restored their calcium (Ca2+) mobilization capacity, led to downregulation of surface pre-BCR, and induced differentiation to BCR+ cells. Together, our results suggest that the adaptor proteins LAT and SLP-76 are involved in pre-BCR signaling, thereby rescuing arrested murine SLP-65(-/-) pre-B cells.
Su
Yu-wen
YW
Institute for Biology III, Albert-Ludwigs University of Freiburg and Max Planck Institute for Immunobiology, Freiburg, Germany.
Jumaa
Hassan
H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051925:CD79 Antigens; D020013:Calcium Signaling / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D015536:Down-Regulation; D066298:In Vitro Techniques; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C113939:B cell linker protein; D051925:CD79 Antigens; D002352:Carrier Proteins; C497882:Cd79a protein, mouse; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D010738:Type C Phospholipases; D051966:Phospholipase C gamma