Complement activation is not required for IgG‐mediated suppression of the antibody response

Birgitta Heyman, Erik Wiersma, Masato Nose

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Feedback suppression of the antibody response by IgG is known to be dependent on intact Fc regions. However, it is not clear which of the Fc‐mediated effector functions is required. In the present report we have studied whether ability or inability of the IgG antibodies to activate the complement system was of consequence for their immunosuppressive effect First, a monoclonal IgG1‐anti‐2,4,6‐trinitrophenyl (TNP) antibody, unable to activate complement via the classical or alternate pathway, was shown to be able to inhibit more than 90% of the in vivo sheep erythrocyte‐specific antibody response in mice when TNP coupled to sheep erythrocytes was used as antigen Second, we investigated the immunosuppressive ability of a non‐complement‐activating mutant IgG2a,‐anti‐TNP monoclonal antibody. The mutant differs from the wild type by a single amino acid substitution in the CH2 domain leading to inability to fix complement factor Clq. However, the mutant has the same affinity for antigen and the same Fc receptor‐binding capacity as the wild type antibody. It is demonstratd that the mutant was as efficient as the wild type antibody in inhibiting an in vitro antibody response to TNP‐coupled sheep erythrocytes These findings confirm the non‐determinant specificity and Fc dependence of IgG‐mediated suppression, and show that the Fc‐mediated effector mechanism is independent of complement activation. The results instead suggest binding to Fc receptors as a necessary step in feedback immunosuppression and favor inactivation of B cells by cross‐linking of Fc and antigen receptors on their surface rather than elimination of antigen by complement‐dependent phagocytosis as the effector mechanism.

Original languageEnglish
Pages (from-to)1739-1744
Number of pages6
JournalEuropean Journal of Immunology
Volume18
Issue number11
DOIs
Publication statusPublished - 1988 Nov
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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