Induction of Self-Rolerance in T Cells But Not B Cells of Transgenic Mice Expressing Little Self Antigen

Abstract

Self-tolerance to a transgene-encoded protein, hen egg lysozyme, was examined in the T and B cell repertoires of a series of lines of transgenic mice that expressed different serum concentrations of soluble lysozyme. T cells were tolerant in all lines in which lysozyme was expressed irrespective of the antigen concentration, whereas B cell tolerance did not occur when the serum lysozyme concentration was less than 1.5 nanograms per milliliter (0.1 nM). Induction of elevated transgene expression could restore B cell tolerance. These findings support the hypothesis that autoimmune disease may in some instances arise through a bypass of T cell tolerance.

CD25+ Treg specifically suppress auto‐Ab generation against pancreatic tissue autoantigens

“…Auto-Ab production by autoreactive B cells that survive these checkpoints can be avoided by extrinsic regulation [1], like the absence of T cell help resulting from central T-cell tolerance, which appears to be more efficient than central B-cell tolerance [12]. Th cells are required for B-cell survival [1], class switching, Ig synthesis and somatic hypermutation [6,13,14].…”

“…Anergic B cells are arrested in the transitional T2 developmental stage, followed by their death [10]. B cells also die in response to continuous antigen binding [11] and BCR signaling [9].Auto-Ab production by autoreactive B cells that survive these checkpoints can be avoided by extrinsic regulation [1], like the absence of T cell help resulting from central T-cell tolerance, which appears to be more efficient than central B-cell tolerance [12]. Th cells are required for B-cell survival [1], class switching, Ig synthesis and somatic hypermutation [6,13,14].…”

Breakdown of Tolerance to a Neo-Self Antigen in Double Transgenic Mice in Which B Cells Present the Antigen

“…Likewise, no HEL could be detected in the serum of our HEL-Tg mice when using a method with a threshold of 1 ng/ml (15). It is noteworthy, however, that the HEL-Tg mice used to generate the DBL-Tg mice in our study resembled the Tg mice with high levels of soluble HEL in the study of Goodnow's group (13) in showing both cellular (Fig. 3A) and humoral ( Fig.…”

“…5 and 10). Their research employed double-Tg ("Dbl-Tg") mice generated by mating Tg mice in which hen egg lysozyme (HEL) was present ubiquitously (11)(12)(13) or in a single organ (14), with Tg mice in which the majority of B cells produced surface-bound and secreted Abs against this Ag ("Ig-Tg" mice). However, little information has been collected in these studies concerning the fate of T cells and the mode whereby Dbl-Tg mice respond to immunization with HEL.…”

Continuous inhibitory signaling by both SHP-1 and SHIP-1 pathways is required to maintain unresponsiveness of anergic B cells

“…However, it is widely assumed that under normal conditions autoimmunity does not occur because T cells of relevant autoantigen specificity are deleted in the thymus (Adelstein et al, 1991). It is intriguing that immediately before proliferation, SHIP-1-deficient Ars/A1 B cells express elevated levels of MHC class II and CD86 consistent with subsequent productive interaction with CD4 T cells.…”