Effect of anti-alkaline phosphatase monoclonal antibody on B lymphocyte function.
Alkaline phosphatase (APase) is a glycosylphosphatidyl-inositol (GPI)-anchored protein appearing on the membranes of mitogen-stimulated B cells after progression into S phase of the cell cycle. Maximal APase expression occurs after peak proliferation and precedes maximal immunoglobulin (Ig) secretion. While APase is clearly an activation marker for mitogen-stimulated B cells, the physiologic role of APase in B cells has not been defined. Other GPI-anchored proteins have been assigned roles in transmembrane signaling since treatment with specific monoclonal antibodies (mAbs) can modulate and/or mimic the effect of mitogens or antigens. Thus, as an initial attempt to determine whether membrane APase (mAPase) plays a role in B cell activation, rat splenic B cells were treated with anti-APase specific mAb in the presence and absence of LPS plus dextran sulfate, known B cell mitogens. Anti-APase mAb alone did not induce proliferation or modulate mitogen-induced proliferation as measured by [3H]thymidine uptake and viable cell recoveries. However, the mAb augmented IgM secretion when used in a soluble form or cross-linked with anti-Ig. Both soluble and immobilized anti-APase mAb decreased the expression of APase activity by mitogen-stimulated B cells. Based upon these results we propose: (1) that transmembrane signaling may occur through mAPase as described for other GPI-anchored proteins such as Thy-1, CD55, CD59, CD24, CD73, Fc gamma III, Qa-2, Ly-6A/E and LFA-3, and (2) this signaling may be regulated by changes in protein phosphorylation caused by modulation of cellular phosphatases, specifically APase.
Marty
L M
LM
V.A. Lakeside Medical Center, Chicago, IL 60611.
Feldbush
T L
TL
D000469:Alkaline Phosphatase / Q000276:immunology* / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000201:enzymology / Q000502:physiology*; D002478:Cells, Cultured; D016264:Dextran Sulfate / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007075:Immunoglobulin M / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D016264:Dextran Sulfate; D000469:Alkaline Phosphatase