HAPTEN-SPECIFIC IgE ANTIBODY RESPONSES IN MICE

Abstract

The present studies have established conditions for the demonstration of cooperative interactions between specific T and B lymphocyte populations in the development of IgE antibody responses in vivo in mice. This has been accomplished by utilizing a system which permits the successful adoptive transfer to irradiated recipients of DNP-specific secondary IgE responses with spleen cells from suitably primed syngeneic donor mice. Thus, adoptively transferred DNP-KLH or DNP-ASC-primed spleen cells produced high levels of anti-DNP antibodies of both IgE and IgG antibody classes in response to challenge with the appropriate homologous priming conjugate but failed to develop more than meager responses to the reciprocal heterologous conjugate. However, when spleen cells from donors primed to the second carrier were concomitantly transferred with hapten-primed lymphocytes, secondary IgE ant-DNP responses were consistently obtained upon challenge with the heterologous conjugate. Moreover, we have been able to elicit augmented primary IgE anti-DNP antibody responses to either DNP-ASC or DNP-KLH after adoptive transfer of spleen cells from donors primed only to the carrier, ASC or KLH, respectively. This adoptive transfer system has enabled us to provide direct proof for the participation of θ-bearing T lymphocytes in antibody responses of the IgE class. Thus, the capacity of ASC-primed spleen cells to effectively cooperate with the DNP-KLH-primed lymphocytes in the adoptive secondary response to DNP-ASC could be abolished by in vitro treatment of such cells with anti-θ serum plus complement. This was true not only for the anti-DNP response of the IgG antibody class, but for the IgE antibody class as well. These studies have, furthermore, demonstrated the capacity to stimulate secondary anti-DNP antibody production in vivo by the concomitant administration of the DNP and relevant carrier determinants on separate molecules. This was more readily seen in the IgE than in the IgG antibody class. Thus, DNP-ASC-primed cells developed significant IgE, but more variable IgG, anti-DNP responses upon challenge with DNP-KLH plus unconjugated ASC. Antibody responses of both classes elicited in this manner were appreciably improved by the transfer of additional carrier (ASC)-primed cells. These and other results presented herein suggest that IgE B lymphocyte precursors may be inherently more sensitive than IgG B cells to at least certain of the functions of T lymphocytes concerned with regulatory mechanisms involved in antibody production.

CD8+ T cells in allergy

“…Their observations were confirmed by others who showed that animals depleted of T cells were unable to produce primary IgE responses (76,77). Ongoing IgE responses were also shown to require continued T cell help, as injection of mice infested with the netnatode Nippostrongylus braziliensis with anti-CD4 antibodies suppressed ongoing IgE production (78).…”

Induction of T-lymphocyte responses to a small molecular weight antigen. III. T-T cell interactions to determinants linked together: suppression vs. enhancement.

“…This is not however, an absolute requirement since under certain conditions the induction of secondary antihapten antibody responses can be accomplished by administration of hapten and carrier determinants on separate molecules (13,14) . The preferential stimulation of cooperative T-B cell interactions by linked determinants raises the question of whether T-T cell interactions of the type being studied here would follow the same pattern .…”

Mechanism of T-cell help in the immune response to soluble protein antigens. I. Evidence for in situ generation and action of T-cell-replacing factor during the anamnestic response to dinitrophenyl keyhole limpet hemocyanin in vitro.

“…On the other hand, Hamaoka et al (37) found a stimulation of anti-hapten IgE responses in vivo al~er transfer of DNP Ascaris-primed mouse cells and challenge with DNP-KLH in the presence of free Ascaris carrier. A very weak anit-hapten IgG response was also observed provided additional Ascaris-primed helper cells were transferred.…”