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Regulation of MHC class II signal transduction by the B cell coreceptors CD19 and CD22.
J Immunol. 2000 Nov 15; 165(10):5588-96.JI

Abstract

The major histocompatability class II heterodimer (class II) is expressed on the surface of both resting and activated B cells. Although it is clear that class II expression is required for Ag presentation to CD4(+) T cells, substantial evidence suggests that class II serves as a signal transducing receptor that regulates B cell function. In ex vivo B cells primed by Ag receptor (BCR) cross-linking and incubation with IL-4, or B cell lines such as K46-17 micromlambda, class II ligation leads to the activation of protein tyrosine kinases, including Lyn and Syk and subsequent phospholipase Cgamma-dependent mobilization of Ca(2+). In this study, experiments demonstrated reciprocal desensitization of class II and BCR signaling upon cross-linking of either receptor, suggesting that the two receptors transduce signals via common processes and/or effector proteins. Because class II and BCR signal transduction pathways exhibit functional similarities, additional studies were conducted to evaluate whether class II signaling is regulated by BCR coreceptors. Upon cross-linking of class II, the BCR coreceptors CD19 and CD22 were inducibly phosphorylated on tyrosine residues. Phosphorylation of CD22 was associated with increased recruitment and binding of the protein tyrosine phosphatase SHP-1. Similarly, tyrosine phosphorylation of CD19 resulted in recruitment and binding of Vav and phosphatidylinositol 3-kinase. Finally, co-cross-linking studies demonstrated that signaling via class II was either attenuated (CD22/SHP-1) or enhanced (CD19/Vav and phosphatidylinositol 3-kinase), depending on the coreceptor that was brought into close proximity. Collectively, these results suggest that CD19 and CD22 modulate class II signaling in a manner similar to that for the BCR.

Authors+Show Affiliations

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11067914

Citation

Bobbitt, K R., and L B. Justement. "Regulation of MHC Class II Signal Transduction By the B Cell Coreceptors CD19 and CD22." Journal of Immunology (Baltimore, Md. : 1950), vol. 165, no. 10, 2000, pp. 5588-96.
Bobbitt KR, Justement LB. Regulation of MHC class II signal transduction by the B cell coreceptors CD19 and CD22. J Immunol. 2000;165(10):5588-96.
Bobbitt, K. R., & Justement, L. B. (2000). Regulation of MHC class II signal transduction by the B cell coreceptors CD19 and CD22. Journal of Immunology (Baltimore, Md. : 1950), 165(10), 5588-96.
Bobbitt KR, Justement LB. Regulation of MHC Class II Signal Transduction By the B Cell Coreceptors CD19 and CD22. J Immunol. 2000 Nov 15;165(10):5588-96. PubMed PMID: 11067914.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of MHC class II signal transduction by the B cell coreceptors CD19 and CD22. AU - Bobbitt,K R, AU - Justement,L B, PY - 2000/11/9/pubmed PY - 2001/2/28/medline PY - 2000/11/9/entrez SP - 5588 EP - 96 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 165 IS - 10 N2 - The major histocompatability class II heterodimer (class II) is expressed on the surface of both resting and activated B cells. Although it is clear that class II expression is required for Ag presentation to CD4(+) T cells, substantial evidence suggests that class II serves as a signal transducing receptor that regulates B cell function. In ex vivo B cells primed by Ag receptor (BCR) cross-linking and incubation with IL-4, or B cell lines such as K46-17 micromlambda, class II ligation leads to the activation of protein tyrosine kinases, including Lyn and Syk and subsequent phospholipase Cgamma-dependent mobilization of Ca(2+). In this study, experiments demonstrated reciprocal desensitization of class II and BCR signaling upon cross-linking of either receptor, suggesting that the two receptors transduce signals via common processes and/or effector proteins. Because class II and BCR signal transduction pathways exhibit functional similarities, additional studies were conducted to evaluate whether class II signaling is regulated by BCR coreceptors. Upon cross-linking of class II, the BCR coreceptors CD19 and CD22 were inducibly phosphorylated on tyrosine residues. Phosphorylation of CD22 was associated with increased recruitment and binding of the protein tyrosine phosphatase SHP-1. Similarly, tyrosine phosphorylation of CD19 resulted in recruitment and binding of Vav and phosphatidylinositol 3-kinase. Finally, co-cross-linking studies demonstrated that signaling via class II was either attenuated (CD22/SHP-1) or enhanced (CD19/Vav and phosphatidylinositol 3-kinase), depending on the coreceptor that was brought into close proximity. Collectively, these results suggest that CD19 and CD22 modulate class II signaling in a manner similar to that for the BCR. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/11067914/Regulation_of_MHC_class_II_signal_transduction_by_the_B_cell_coreceptors_CD19_and_CD22_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=11067914 DB - PRIME DP - Unbound Medicine ER -