Regulation of B cell:T cell interactions: potential involvement of an endogenous B cell sialidase.
In light of the ability of B cells treated with neuraminidase to interact more effectively with T cells, the increased capacity of activated, but not small resting B cells, to interact with T cells could be associated with the level of sialylation on certain B cell surface molecules which influences the effectiveness of the physical interaction between B and T cells. The purpose of this study was to determine if activation of B cells altered sialylation via an endogenous sialidase which affected both the initial interaction between T and B cells and subsequent B cell-induced T cell proliferation. The competitive neuraminidase inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NeuAc2en), inhibited LPS-mediated enhancement of B cell conjugate formation with Ia-specific T cell clones as well as enhancement of their capacity to stimulate a mixed lymphocyte reaction. The addition of NeuAc2en during LPS stimulation did not affect the surface expression of Ia, LFA-1, ICAM-1 or mB7, suggesting that inhibition of LPS-mediated enhancement by the sialidase inhibitor was not due to changes in the level of expression of the major B cell adhesion or co-stimulatory molecules. Short term stimulation with phorbol myristate acetate (PMA) and ionomycin also enhanced the ability of resting B cells to form antigen specific T:B conjugates. However, activation of B cells with PMA and ionomycin or with LPS did not change the capacity of a sialic acid specific lectin to bind to the B cells, suggesting that activation was not associated with global changes in surface sialic acid content. B cell stimulation did not appear to increase the activity of the most prevalent B cell sialidase activity as measured in an in vitro assay system, suggesting that the major B cell sialidase may not be responsible for the alteration of B cell sialylation levels or the ability of activated B cells to interact more effectively with T cells. The possibility of intracellular compartmentalization of sialidase activity or that a minor B cell sialidase may play a role in the regulation of a B cells ability to interact with T cells are discussed.
Guthridge
J M
JM
Department of Microbiology and Immunology, Albert B. Chandler Medical Center, University of Kentucky, Lexington 40536-0084.
Kaplan
A M
AM
Cohen
D A
DA
D000818:Animals; D001386:Azides / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000502:physiology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase / Q000502:physiology*; D012794:Sialic Acids / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology*
D001386:Azides; D008070:Lipopolysaccharides; D012794:Sialic Acids; C064632:5-N-acetyl-9-(4-azidosalicoylamido)-2-deoxy-2,3-didehydroneuraminic acid; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid