PU.1 and Spi-B are required for normal B cell receptor-mediated signal transduction.
PU.1 and Spi-B have previously been implicated in the regulation of genes encoding B cell receptor (BCR) signaling components. Spi-B-/- B lymphocytes respond poorly to BCR stimulation; PU.1-/- mice, however, lack B cells, precluding an analysis of BCR responses. We now show that PU.1+/- Spi-B-/- B cells exhibit more extensive defects than Spi-B-/- B cells, indicating that both PU.1 and Spi-B are required for normal BCR signaling. Strikingly, BCR cross-linking results in substantially reduced protein tyrosine phosphorylation in mutant B cells. Further analysis shows that Igalpha is phosphorylated and syk is recruited and becomes phosphorylated but that BLNK and PLCgamma phosphorylation are defective in mutant cells. Our data support the existence of a novel component coupling syk to downstream targets.
Garrett-Sinha
L A
LA
Howard Hughes Medical Institute, University of Chicago, Illinois 60637, USA.
Su
G H
GH
Rao
S
S
Kabak
S
S
Hao
Z
Z
Clark
M R
MR
Simon
M C
MC
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D020013:Calcium Signaling / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000502:physiology; D050835:Interferon Regulatory Factors; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D011947:Receptors, Antigen, B-Cell; D015534:Trans-Activators; D014157:Transcription Factors; D014443:Tyrosine; D000099218:Interferon Regulatory Factor-4; C076877:SPIB protein, human