Absence of an antigen‐specific helper T cell required for the expression of the Tn 15 idiotype in mice treated with anti‐μ antibody

Abstract

T‐dependent anti‐phosphorylcholine (PC) plaque‐forming cell (PFC) responses were studied in BALB/c mice. Helper T cells derived from normal, carrier‐primed donors induced anti‐PC PFC responses dominated by the T15 idiotype. Helper T cells derived from carrier‐primed mice that had been treated from birth with anti‐μ antibody, so that they were lacking B cells and circulating antibody bearing the T15 idiotype, also provided helper cell function for the anti‐PC antibody response. In contrast to the response induced by helper T cells from normal mice, T helper cells from μ‐suppressed mice induced an anti‐PC antibody response which was mainly non‐ T15 in character. The failure to induce antibody formation by T15+ B cells was not due to suppressor cells but rather to the lack of an Lyt‐1+ helper T cell population which is necessary for predominant T15 production. This latter cell population was shown to be present in carrier‐primed normal but missing or diminished in carrier‐ primed anti‐μ‐treated BALB/c mice. It required carrier priming for the expression of its helper function, but its function did not require the antigen (carrier) to be physically linked to the hapten. From this, we conclude that dominant production of the T15 idiotype involves the synergistic activity of two antigen‐specific helper T cells. The helper cell population which is required for predominant T15 production is greatly diminished in mice treated with anti‐μ antibody from birth. Hence, the production of circulating T15+ antibody induced by environmental antigens or the appearance of T 15‐bearing B cells would appear to be required for the induction of helper T cells which enhance T15+ anti‐PC antibody synthesis.

Antigen-specific helper T cells required for dominant production of an idiotype (THId) are not under immune response (Ir) gene control.

“…It has been previously established that the dominant production of T 15 idiotype in the antibody response to PC-proteins requires two distinct Th (11,12). One Th cell set is present in both carrier-primed normal mice and mice treated from birth with anti-/z antibody.…”

“…The second Th set is present in normal BALB/c mice but lacking in carrier-primed anti-/z suppressed mice, and it is necessary for predominant production of the T15 idiotype. The missing T cell set necessary for T15 production in anti-/t suppressed BALB/c mice can be restored by adding carrier-primed T cells from normal BALB/c donors along with the priming antigen (12).…”

“…This antibody reacted only with IgM in normal mouse serum by immunoelectrophoresis. The anti-/x-treated mice had no surfaceimmunoglobulin-positive cells in their spleens and no circulating T15 idiotype at the time of killing (12).…”

Modulation of Tthy alloantigen expression in the neonatal mouse. The Tthy-bearing thymocyte is a precursor for the peripheral cells expressing Tind and Tsu.

“…Thus, Bottomly et al (11) have shown that treatment of newborn mice with anti-# antibody leads to the disappearance of not only sIg + B lymphocytes but also an antigen-specific T helper cell required for the expression of the T15 idiotype. Similarly, studies by Fultz and co-workers (23) have indicated that chronic suppression of an IA k specificity results in the depletion of surface IgM + B lymphocytes as well as significantly decreased MLR responses.…”

“…Mice were injected intraperitoneally with 10 /Lg antibody within 24 h of birth. Injections were continued at 48 -h intervals until the mice were killed between days 35 and 45, mimicking the protocol used to deplete/l-bearing B cells (2,11).…”