The therapeutic implications of activated immune responses via the enigmatic immunoglobulin D

Abstract

Immunoglobulin D (IgD) is an enigmatic antibody and the least appreciated member of the immunoglobulin (Ig) family. Since its discovery over half a century ago, the essence of its function in the immune system has been somewhat enigmatic and less well-defined than other antibody classes. Membrane-bound IgD (mIgD) is mostly recognized as B-cell receptor (BCR) while secreted IgD (sIgD) has been recently implicated in ‘arming’ basophils and mast cells in mucosal innate immunity. Activations of immune responses via mIgD-BCR or sIgD by specific antigens or anti-IgD antibody thereby produce a broad and complex mix of cellular, antibody and cytokine responses from both the innate and adaptive immune systems. Such broadly activated immune responses via IgD were initially deemed to potentiate and exacerbate the onset of autoimmune and allergic conditions. Paradoxically, treatments with anti-IgD antibody suppressed and ameliorated autoimmune conditions and allergic inflammations in mouse models without compromising the host’s general immune defence, demonstrating a unique and novel therapeutic application for anti-IgD antibody treatment. Herein, this review endeavored to collate and summarize the evidence of the unique characteristics and features of activated immune responses via mIgD-BCR and sIgD that revealed an unappreciated immune-regulatory function of IgD in the immune system via an amplifying loop of anti-inflammatory Th2 and tolerogenic responses, and highlighted a novel therapeutic paradigm in harnessing these immune responses to treat human autoimmune and allergic conditions.

Keywords:

• Allergy
• autoimmune diseases
• basophils
• B-cell receptor
• B cells
• IgD
• immune tolerance
• immunotherapy
• mast cells
• regulatory B cells

Acknowledgements

The prime purpose of this review was to summarize the evidence and highlight the arguments and new understandings for the proposed concept in the article. Due to the format limit, it was unable to reference exhaustively all relevant literatures. The author acknowledges all relevant works by other studies that may not have been included in this review.

Disclosures

Dr TG Nguyen is the founder of IgD Mab Technology (IMT) group and has been named as the leading inventor on granted patents related to the therapeutic applications of Methods of anti-IgD antibody (WO2007124529A1).