Antibody Polyreactivity in Health and Disease: Statu Variabilis

Abstract

An Ab molecule or a BCR that is able to bind multiple structurally unrelated Ags is defined as polyreactive. Polyreactive Abs and BCRs constitute an important part of immune repertoires under physiological conditions and may play essential roles in immune defense and in the maintenance of immune homeostasis. In this review, we integrate and discuss different findings that reveal the indispensable role of Ag-binding polyreactivity in the immune system. First, we describe the functional and molecular characteristics of polyreactive Abs. The following part of the review concentrates on the biological roles attributed to polyreactive Abs and to polyreactive BCRs. Finally, we discuss recent studies that link Ig polyreactivity with distinct pathological conditions.

Chlamydophila psittaci-negative ocular adnexal marginal zone lymphomas express self polyreactive B-cell receptors

“…42 It is presently unknown whether the visualized macrophages, localized in close proximity to the lymphoma cells, presented galectin-3 to lymphoma cells or simply expressed this known marker of macrophage activation. 43 Polyreactive Abs can be germline or affinity matured, 44 in agreement with BCRs derived from OAEMZLs. In healthy individuals, only about 4% of circulating naive B cells express polyreactive Abs.…”

Serology in the 21st century: the molecular-level analysis of the serum antibody repertoire

“…Second, while it is well established that a significant fraction of antibodies display polyreactivity and that these antibodies have important physiological functions in processes such as the clearance of cell debris and in pathogen recognition[24,25], there is a paucity of methods for quantifying and characterizing the polyreactive fraction of the serological response. It is noteworthy that, in addition to natural antibodies, which are typically polyreactive, IgG antibodies encoded by human memory B cells [26] and even bone marrow plasma cells and also bNAbs elicited by anti-viral immune responses in response to HIV-1 infection [27] often recognize multiple antigens.…”

“…The polyspecific antibody repertoire : As mentioned above, the immunological significance of antibody polyreactivity or polyspecificity is being increasingly appreciated [24,70]. However, polyspecificity as a feature of the serum antibody response has not been investigated in a systematic way.…”

A Cryptic Polyreactive Antibody Recognizes Distinct Clades of HIV-1 Glycoprotein 120 by an Identical Binding Mechanism

“…These Abs are defined as polyreactive (1). The polyreactivity of Abs and B cell receptors is believed to contribute to the diversification of the immune repertoire and endows the immune system with the ability to bind, and respond, to virtually any potential antigen at a given time (2)(3)(4). Circulating polyreactive Abs found under physiological conditions, especially those also present in preimmune repertoires, have been proposed to constitute a first line of defense against pathogens and to participate in the maintenance of immune homeostasis (1,(5)(6)(7)(8).…”