Tyrosine phosphorylation of CD19 in pre-B and mature B cells.
Cross-linking of B cell surface immunoglobulins (sIg) results in activation of mature B cells and stimulates a molecular signaling mechanism for antigen-specific B cell expansion and differentiation. This signaling pathway is dependent on tyrosine (Tyr) phosphorylation and results in the activation of sIg-associated src family kinases and p72SYK. Rapid Tyr phosphorylation occurs on multiple protein substrates. Here we show that activation of B cells by cross-linking sIg results in an increase in Tyr phosphorylation of the lineage-restricted B cell surface antigen CD19, and show that it is a major substrate of activated Tyr kinase following sIg stimulation. Lower levels of constitutive CD19 Tyr phosphorylation occurred in most sIg+ mature B cell lines examined and in normal dense tonsillar B cells. We also find that when CD19 is Tyr-phosphorylated it becomes competent to interact with SH2 domains suggesting a mechanism whereby, following B cell activation, CD19 could be linked to intracellular signaling pathways. In sIg- pre-B cell lines, CD19 was expressed but was not constitutively phosphorylated on tyrosine. Upon CD19 cross-linking, Tyr phosphorylation of CD19 was induced in sIg- pre-B cell lines. CD19 cross-linking also directly induced Tyr phosphorylation of CD19 and other substrates in mature B cells. The ability of CD19 to signal in the absence of sIg expression may provide important stimulation in pre-B cell development.
Chalupny
N J
NJ
Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, WA 98121.
Kanner
S B
SB
Schieven
G L
GL
Wee
S F
SF
Gilliland
L K
LK
Aruffo
A
A
Ledbetter
J A
JA
D015703:Antigens, CD / Q000378:metabolism*; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D003432:Cross-Linking Reagents; D006801:Humans; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D003432:Cross-Linking Reagents; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine