Modulation of B lymphocyte antigen receptor signal transduction by a CD19/CD22 regulatory loop.
CD19 and CD22 are B lymphocyte cell-surface molecules that positively and negatively regulate antigen receptor signal transduction, respectively. Biochemical studies with B cells from CD19-deficient and CD22-deficient mice indicated that these two regulatory molecules influenced each other's functions: CD22 expression negatively regulated CD19 tyrosine phosphorylation, while optimal CD22 function was dependent on CD19 expression. Functional CD19 and CD22 interactions were also assessed in vivo by generating CD19/CD22 double-deficient mice. Remarkably, the CD19 mutation was dominant to the CD22 mutation in most instances. B lymphocytes from CD19/CD22-deficient and CD19-deficient mice were functionally equivalent despite the negative influence normally provided by CD22 expression. These data collectively suggest that CD19 activates the CD22/SHP1 inhibitory pathway that then acts primarily on CD19.
Fujimoto
M
M
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Bradney
A P
AP
Poe
J C
JC
Steeber
D A
DA
Tedder
T F
TF
D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000502:physiology*; D018941:Antigens, CD19 / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D015815:Cell Adhesion Molecules; D007075:Immunoglobulin M / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D051379:Mice; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000032:analysis / Q000502:physiology*; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D014443:Tyrosine; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D002118:Calcium