Clonal anergy: Persistence in tolerant mice of antigen-binding B lymphocytes incapable of responding to antigen or mitogen

Abstract

The purpose of these experiments was to determine the degree of reduction in the number of antigenbinding B lymphocytes in the spleens of mice that had been rendered tolerant in the perinatal period. Newborn or pregnant mice were injected with fluorescein (Flu) coupled onto human gamma globulin, and the spleen cells of the neonatally injected mice, or of the offspring of the pregnant mice, were analyzed 1-6 weeks later. Tolerogen doses were chosen so as to achieve either a two-thirds reduction (low dose) in the number of anti-Flu B cells capable of yielding anti-hapten plaque-forming cell clones after in vitro stimu ation, or as representing a supraoptimal tolerogenic stimulus (high dose). Antigen-binding B cells were studied by a two-cycle procedure, namely an initial cycle of binding to Flu-gelatin (about 30% of the Flu-gelatin-binding number) was then subtracted from the Flu-gelatin-binding number of the identical group to arrive at a net figure for Flu-binding cells.

B Cells from Mice Prematurely Expressing Human Complement Receptor Type 2 Are Unresponsive to T-Dependent Antigens

“…Anergy is thought to arise as the immature B cells leave the bone marrow and enter the periphery (12,42,43). If they meet Ags without the appropriate T cell help (CD40 Ligand), they are anergized or deleted.…”

BAFF and the plasticity of peripheral B cell tolerance

“…These notions, originally proposed by Nossal and Pike [3,4], were apparently supported by in vivo studies in the HEL/anti-HEL transgenic model, where high avidity BCR interactions led to the elimination of HEL-reactive cells in the bone marrow, while low avidity interactions indeed yielded self-reactive cells in the periphery [5]. However, following description of the TR compartment, Fulcher and Basten demonstrated that these 'anergic' B cells achieved entrance to the TR pools, but nonetheless died rapidly before entering mature pools [6].…”

Biological therapy: approaches in colorectal cancer

“…Co-stimulatory signals implicated in the activation of the TcR include tyrosine kinases, interleukins, the B7 family (Chen et al, 1993) (Nossal and Pike, 1980;Goodnow et al, 1991). The concept of a population of down-regulated T-and B-cell repertoires with a threshold affinity for silencing was advanced by Nossal (1983) as one of 'immune ignorance'.…”