CD19 and CD22 expression reciprocally regulates tyrosine phosphorylation of Vav protein during B lymphocyte signaling.
B cell development and humoral immune responses are controlled by signaling thresholds established through the B lymphocyte antigen receptor (BCR) complex. BCR signaling thresholds are differentially regulated by the CD22 and CD19 cell surface receptors in vivo. B cells from CD22-deficient mice exhibit characteristics of chronic stimulation and are hyper-responsive to BCR crosslinking with augmented intracellular Ca2+ responses. By contrast, B cells from CD19-deficient mice are hypo-responsive to transmembrane signals. To identify signaling molecules involved in the positive and negative regulation of signaling thresholds, the signal transduction pathways activated after BCR crosslinking were examined in CD22- and CD19-deficient B cells. These comparisons revealed that tyrosine phosphorylation of Vav protein was uniquely augmented after BCR or CD19 crosslinking in CD22-deficient B cells, yet was modest and transient after BCR crosslinking in CD19-deficient B cells. Ligation of CD19 and CD22 in vivo is likely to positively and negatively regulate BCR signaling, respectively, because CD19 crosslinking was more efficient than BCR crosslinking at inducing Vav phosphorylation. However, simultaneous crosslinking of CD19 with the BCR resulted in a substantial decrease in Vav phosphorylation when CD22 was expressed. Thus, the differential regulation of Vav tyrosine phosphorylation by CD19 and CD22 may provide a molecular mechanism for adjusting BCR signaling thresholds.
Sato
S
S
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Jansen
P J
PJ
Tedder
T F
TF
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D018941:Antigens, CD19 / Q000235:genetics*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics*; D001402:B-Lymphocytes / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D037102:Lectins; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism*
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D037102:Lectins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D051918:Sialic Acid Binding Ig-like Lectin 2; C496619:Vav1 protein, mouse; D014443:Tyrosine