Inhibition of an IgE response by secondary B cells of a different isotype.

Abstract

Under certain circumstances, secondary B cells can preempt an immune response and inhibit the expression of the products of primary B cells having the same specificity. This effect was illustrated by experiments (1) that made use of a major intrastrain crossreactive idiotype characteristic of the anti-Ars antibodies of strain A mice (CRI A)' . The idiotype is absent in the anti-Ars antibodies of BALB/c mice (H-2" ; Igha), but present in allotype-congenic GAL-20 mice (H-2", Igh" ; references 1, 2). After transfer of lymphocytes from Ars-immune BALB/c mice to mildly irradiated (200 rad) nonimmune GAL-20 recipients, the latter produced no CRIA+ antibodies after immunization with KLH-Ars . It was shown (1) that the inhibition of CRIA expression was mediated by the B cells of the donor and that T cells were ineffective. A possible synergistic effect of small amounts of contaminating carrier-specific Ts cells was ruled out by using different carriers for the hapten in the donor and recipient mice . The inhibition was shown to persist for at least 5 mo after an adoptive transfer . Similar experiments were carried out (3) by using A/J mice as a source of lymphoid cells for adoptive transfer . These donor mice were idiotypically suppressed for CRIA and then immunized. Mildly irradiated A/J mice that received either enriched B or T cells from such donors expressed little or no CRI A upon subsequent immunization against the Ars hapten . On a numerical basis, B cells were somewhat more suppressive than T cells.Experiments of similar design indicated that this effect can be used to suppress an allotype as well as an idiotype (4) . Spleen cells from BALB/c mice immunized with KLH-TNP were adoptively transferred into irradiated (200 rad) allotypecongenic partners (C .B-17), which were then immunized to TNP . Through day 58 after the adoptive transfer, ?80% of the IgG antibody produced was of donor allotype . By day 110, the allotype of the host dominated in most but not all recipients . Other recipients that were given nonimmune BALB/c cells produced antibodies almost entirely of the recipients' allotype . The participation of T cells in the suppression was not completely ruled out but appears improbable ; i . e., it seems unlikely that immunized BALB/c mice would produce Ts cells specific for an unrelated allotype . An explanation consistent with each set of results discussed This work was supported by National Institutes of Health grants AI-22068 and AI-24272 . M . F. Gurish was supported by a postdoctoral fellowship from the Arthritis Foundation .' Abbreviation used in this paper: CRIA, a major intrastrain crossreactive idiotype characteristic of the anti-Ars antibodies of strain A mice . 2018J . Exp. MED.