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CD54/intercellular adhesion molecule 1 and major histocompatibility complex II signaling induces B cells to express
1Department of Medicine, McGill University, Montreal, Quebec, Canada.
Insights
CD54 and MHC II act as contact ligands, complementing CD40 signaling for T-dependent B cell activation and IL-2 responsiveness. This study reveals their crucial roles in B cell differentiation and Ig secretion.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Signaling
Background:
- T helper cell interactions are critical for B cell activation and differentiation.
- Intercellular adhesion molecule 1 (CD54) and major histocompatibility complex (MHC) class II molecules are implicated as contact ligands in immune responses.
- CD40 signaling is a key pathway in B cell activation, but its sufficiency for full differentiation is debated.
Purpose of the Study:
- To investigate the signaling roles of CD54 and MHC class II as contact ligands in T helper cell-dependent B cell activation.
- To elucidate the relative contributions of CD54, MHC class II, and CD40 signaling in B cell proliferation and interleukin-2 (IL-2) responsiveness.
- To determine if CD54 and MHC class II can complement CD40 signaling in generating T-dependent B cell responses.
Main Methods:
- Utilized a T helper 1 (Th1)-dependent system for B cell activation.
- Employed paraformaldehyde-fixed activated Th1 cells to induce B cell phenotypic changes.
- Used monoclonal antibodies (mAbs) against CD54 and MHC class II, and a soluble CD40 ligand construct.
- Performed cross-linking experiments of CD54, MHC class II, and CD40 on B cells.
- Assessed B cell proliferation, immunoglobulin (Ig) secretion, and expression of IL-2 receptors (IL-2R) and B7.
Main Results:
- Activated Th1 cells upregulated IL-2R alpha, IL-2R beta, B7, MHC class II, and CD54 on B cells.
- Inhibition of CD54, MHC class II, or CD40 ligand impaired T-dependent Ig secretion and B cell phenotypic changes.
- Cross-linking CD54 and MHC class II mimicked fixed Th1 cell effects on B cell molecules, with co-cross-linking further enhancing B7 expression.
- CD40 ligation induced B cell proliferation but not IL-2 responsiveness.
- Co-ligation of CD54 and MHC class II with IL-5 induced functional IL-2R expression on resting B cells.
Conclusions:
- CD40 ligation is essential but not sufficient for complete B cell differentiation.
- CD54 and MHC class II function as critical contact ligands that synergize with CD40 signaling.
- These contact ligands are crucial for generating T-dependent B cell responses, particularly in inducing responsiveness to IL-2.
Abstract:
We have examined signaling roles for CD54 intercellular adhesion molecule 1 and major histocompatibility complex (MHC) II as contact ligands during T help for B cell activation. We used a T helper 1 (Th1)-dependent helper system that was previously shown to be contact as well as interleukin 2 (IL-2) dependent to demonstrate the relative roles of CD54, MHC II, and CD40 signaling in the events leading to the induction of B cell proliferation and responsiveness to IL-2. Paraformaldehyde-fixed activated Th1-induced expression of IL-2R alpha, IL-2R beta, and B7, and upregulated MHC II and CD54 on B cells. Anti-CD54 and MHC II mAbs as well as a CD8 alpha-CD40 ligand (L) soluble construct inhibited both the T-dependent induction of Ig secretion, and B cell phenotypic changes. We then compared the effects of activated Th1 cells with that of cross-linking these molecules. Cross-linking of CD54 and MHC II resulted in the upregulated expression of MHC II and of CD54 and B7, respectively, analogous to the effect of fixed activated Th1 cells. B7 expression was further enhanced by co-cross-linking CD54 and MHC II. Cross-linking of CD40 achieved comparable effects. Strikingly, cross-linking ligation of CD54 and MHC II in the presence of IL-5 induced expression of a functional IL-2R on small resting B cells. By contrast CD40 ligation, which induced B cell proliferation, did not induce IL-2 responsiveness. These data show that CD40 ligation is necessary but may not be sufficient for B cell differentiation and identify CD54 and MHC II as contact ligands that can complement CD40 signaling in the generation of T-dependent B cell responses to IL-2.