Negligible Class II MHC Presentation of B Cell Receptor-Derived Peptides by High Density Resting B Cells

Abstract

Resting B lymphocytes have been credited with inducing T cell tolerance to Ig-derived and monovalent self-Ags that are internalized via the B cell receptor (BCR). These conclusions are predicated upon the assumptions that resting B cells display BCR-associated peptides in class II MHC and that the cells remain quiescent during the course of experimental manipulation. To determine whether resting B cells display BCR-associated epitopes in class II MHC, we devised a sensitive assay that averted potential activation of B cells by Ag and minimized activation by prolonged culture. Ex vivo, Percoll-fractionated B cells expressing a κ transgene encoding a T cell epitope were cultured with a reactive T cell hybridoma for 12 h. Whereas low density, LPS-activated, and BCR-activated B cells elicited significant IL-2 from the T cell hybridoma, resting high density B cells did not. Parallel results were obtained with normal B cells expressing a second epitope encoded by an endogenous VH gene. Anergic B cells, which are uniformly low density, also significantly stimulated the T cell hybridoma. Finally, longer culture periods with normal B cells resulted in a higher degree of B cell activation and significant stimulation of reactive T cell hybridomas. Our results provide evidence that activation of B cells profoundly enhances the processing and presentation of BCR-associated Ags.

Idiotype-Specific Th Cells Support Oligoclonal Expansion of Anti-dsDNA B Cells in Mice with Lupus

“…B cells express relatively high levels of Id + Ig; Id peptides were among the first to be eluted from MHC class II molecules of B cells (46). Hence, B cells process and present their endogenous BCR as short Id peptides on MHC class II to T cells that may recognize V-region Id peptides (27)(28)(29)(30). It was shown that V regions derived from anti-dsDNA B cells of normal mice (50), as well as BWF1 mice (17,18), contain Id CD4 + T cell epitopes.…”

“…It has been clear for some time that somatically mutated Id peptides can serve as cognate Ags for Th cells (23,24) and that this responsiveness is restricted by tolerance to germline V regions (25,26 (27)(28)(29)(30). In this interaction, B cells can undergo the germinal center reaction, provided that ligands bind the BCR (31).…”

Review: To What Extent are T Cells Tolerant to Immunoglobulin Variable Regions?

“…In the 1980s it became clear that immunoglobulins are processed and presented by antigen-presenting cells (APC) and that V-region-derived Id-peptides are displayed on MHC class II molecules to Id-specific CD4 + T cells [5][6][7][8]. It was further demonstrated that B cells continuously processed their own BCR and constitutively presented Id-peptides on their MHC class II molecules [9][10][11] [12]. Thus, B cells express two types of Id: (1) conformational Id determinants expressed on intact BCR, serologically detected by anti-Id antibodies and (2) short Id-peptides that are presented on MHC class II molecules to Id-specific T cells [9].…”

T Cell Tolerance to Germline-Encoded Antibody Sequences in a Lupus-Prone Mouse

“…Finally, peptides from the BCR V region may provide an avenue of T cell help to autoreactive B cells. The BCR V region is promising in this regard because of the enormous diversity encompassed by V region peptides and because such peptides can be self-presented in class II MHC by activated B cells, which presumably are dependent upon T cell help (25)(26)(27)(28)(29)(30)(31)(32)(33)(34). We refer to this potential avenue of help to autoreactive B cells as the receptor presentation hypothesis (35).…”