The absence of SLP65 and Btk blocks B cell development at the preB cell receptor-positive stage.
Mice deficient for the adapter protein SLP65 (BLNK) show a partial block in early B cell development, reduced numbers of mature B cells in the periphery, an absence of B1 cells and a reduction of IgM and IgG3 serum immunoglobulin levels. A strikingly similar phenotype is observed in Btk-deficient mice. To investigate the consequences of mutations in both SLP65 and Btk, we generated SLP65/ Btk double-mutant mice by crossing the single-mutant mice. Analysis of the double-mutant mice reveals a much more severe defect in B cell development. B cells in the SLP65/Btk double-mutant mice are arrested at the preB cell stage and, surprisingly, express the preB cell receptor. Normally, preB cell receptor expression in wild-type mice is restricted to a very small fraction of B cells making it difficult to identify these cells in the bone marrow. Together, the data demonstrate the synergistic role of SLP65 and Btk in B cell development and describe a situation where large numbers of preB cell receptor-positive cells accumulate in the bone marrow and spleen.
Jumaa
H
H
Molecular Immunology, Biologie III, University of Freiburg and Max Planck Institute for Immunobiology, Freiburg, Germany. jumaa@immunobio.mpg.de
Mitterer
M
M
Reth
M
M
Nielsen
P J
PJ
D048868:Adaptor Proteins, Signal Transducing; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D002454:Cell Differentiation; D017353:Gene Deletion; D051917:Leukosialin; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000032:analysis*; D012795:Sialoglycoproteins / Q000032:analysis; D013154:Spleen / Q000276:immunology; D013234:Stem Cells / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C113939:B cell linker protein; D002352:Carrier Proteins; D051917:Leukosialin; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase