Cognate B Cell Signaling via MHC Class II: Differential Regulation of B Cell Antigen Receptor and MHC Class II/Ig-αβ Signaling by CD22

Abstract

Cognate B Cell Signaling via MHC Class II: Differential Regulation of B Cell Antigen Receptor and MHC Class II/ Ig-
 Signaling by CD221 David M. Mills, John C. Stolpa, and John C. Cambier2 Recent studies demonstrate that MHC class II molecules can signal via associated Ig-
 dimers, signal transducers previously thought to function only in B cell Ag receptor (BCR) signaling. Surprisingly, the biologic outputs of MHC class II and BCR ligation (by thymus-dependent Ags) differ, e.g., MHC class II signaling leads to robust proliferation and extension of pseudopods. It seemed possible that these differences might be due, at least in part, to differential use of inhibitory coreceptors thought to modulate membrane Ig signals. In this study, we demonstrate that CD22, an inhibitory BCR coreceptor, neither associates with nor functions in MHC class II/Ig-
 signaling. Interestingly, CD22 is actively excluded from cell surface MHC class II aggregates. The Journal of Immunology, 2004, 172: 195–201. D uring cognate T cell-B cell interactions, multiple recep- tor-ligand pairs become localized at the cell contact in- terface. Many of these proteins become further ordered into subregions, termed central and peripheral supramolecular ac- tivation clusters (SMACs)3 (1, 2). This organization increases the local concentration of signaling molecules and ensures that certain effectors are sequestered away from some proteins and colocalized with others. Although T cell SMAC formation can occur in the absence of APCs (2), it is currently unknown whether transmem- brane signaling in one or both cells influences the formation, sta- bilization, and movement of molecules into and out of SMACs in vivo. However, although T-B conjugate formation does not depend on the T cell recognizing its specific Ag, the formation of SMACs at cell contact points is seen only upon Ag recognition (1, 2). Thus, Ag-driven aggregation of both MHC class II and TCR may be important for productive T-B collaboration. Ag