Idiotype-anti-idiotype network. II. Activation of silent clones by treatment at birth with idiotypes is associated with the expansion of idiotype-specific helper T cells.

Abstract

BALB/c mice immunized with bacterial levan (BL) produce a vigorous antibody response that fails to include antibodies expressing the idiotype of the beta 2 leads to 6 fructosan-binding myeloma protein ABPC48 (A48). Treatment of newborn BALB/c mice at 1 d of age with 0.1-10 microgram of either the A48 myeloma protein or monoclonal proteins that share idiotopes with the A48 family, followed by immunization with BL 2-4 wk later, produces an anti-BL response that is dominated by the A48Id. Various degrees of activation of the A48Id BL response were observed by injecting mice with A48 monoclonal protein only up until 3 wk of age. Activation of the A48Id clones by treating with A48 monoclonal protein was ineffective in mice who were older than 4 wk. Elicitation of an A48Id BL response required specific antigenic stimulation with either beta 2 leads to 6 or beta 2 leads to 1 fructosan epitopes, because it does not occur after injection with TNP-Ficoll in spite of the A48 treatment. The expansion of A48Id clones in mice treated at birth with A48 monoclonal protein is associated with an increase in A48Id-specific helper T cells. The binding specificity of these cells was demonstrated by infusing them into nu/nu BALB/c mice and observing that they rendered help that enalbed the animal to mount an anti-TNP response after immunization only with A48-TNP, but not with MOPC384-TNP conjugates. The helper activity of these cells is sensitive to the effects of treatment with anti-Lyt-1.2 antibodies plus complement. A predominantly A48Id BL-specific response can be transferred into lethally irradiated mice by infusing them with purified T and B cells from A48-treated mice. The transfer of this response can be ablated by treating the T cells with anti-Lyt-1.2 antibodies plus complement. These results indicate that A48Id-specific helper cells possess the ability to select the A48Id-bearing B cell precursors for expression, thus exerting a fine-tuning effect on the idiotypic expression of the anti-BL repertoire. We propose that this idiotype-induced idiotype response, which can be, in principal, induced by idiotypes provided by the mother, plays an important role in the expansion of precursors of antibody-forming cells during embryonic as well as postnatal life.

Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire.

“…The results presented in this report demonstrate that the extraordinarily high frequency of mature B cells of the T15 clonotype can be accounted for by an equally high frequency of B cells of this clonotype that emerge from the generative cell pool in the bone marrow. Thus, while these findings do not rule out idiotype-specific or antigen-specific selection as contributors to the high frequency of T15 B cells (31,32), they obviate the necessity of such explanations to account for the high frequency of this clonotype. It should be noted that recent investigations using polyclonal stimulation of splenic and immature bone marrow cell populations have led to similar conclusions concerning cells expressing the NP b idiotype in C57BL/6 mice (33) and the 460 idiotype in BALB/c mice (34).…”

Molecular Identification of Pathogenetic IdLNF+1 Autoantibody Idiotypes Derived from the (NZB×SWR)F1 Model for Systemic Lupus Erythematosus

“…In light of pioneering work demonstrating the role of idiotype-specific helper T cells in the upregulation of idiotype-producing B cells [5,6], we sought to examine the role of Id LN F 1 -reactive T cells in the SNF 1 model. The generation of pathogenetic IgG autoantibodies in the SNF 1 mouse is probably due to the activity of autoreactive T cells, since cytokines secreted by T cells mediate isotypic class switching [7].…”

Immune function across generations: integrating mechanism and evolutionary process in maternal antibody transmission

“…Thus, the duration of these maternal effects may far outreach the presence of maternally derived antibodies in offspring. Antibodies administered during the neonatal period of mammals influence the B-cell repertoire expressed after antigenic challenge later in life (mice: Strayer et al 1974;Wikler et al 1980;Rubinstein et al 1982;Elliott & Kearney 1992;rats: Lundin et al 1999). In some cases, maternal antibodies may even affect immune function across multiple generations.…”