Natural Antibody Repertoires: Development and Functional Role in Inhibiting Allergic Airway Disease

Abstract

In this review we discuss the effects of microbial exposure on the B cell repertoire. Neonatal exposure to conserved bacterial carbohydrates and phospholipids permanently reprograms the natural antibody repertoire directed toward these antigens by clonal expansion, alterations in clonal dominance, and increased serum antibody levels. These epitopes are present not only in bacterial cell walls, but also in common environmental allergens. Neonatal immunization with bacterial polysaccharide vaccines results in attenuated allergic airway responses to fungi-, house dust mite-, and cockroach-associated allergens in mouse models. The similarities between mouse and human natural antibody repertoires suggest that reduced microbial exposure in children may have the opposite effect, providing a potential mechanistic explanation for the hygiene hypothesis. We propose that understanding the effects of childhood infections on the natural antibody repertoire and the mechanisms of antibody-mediated immunoregulation observed in allergy models will lead to the development of prevention/interventional strategies for treatment of allergic asthma.

Structural investigation of humanS. aureus-targeting antibodies that bind wall teichoic acid

“…17 Paradoxically, these polysaccharide-reactive antibodies are often somatically hypermutated, which suggests that somatic hypermutation in B cells and subsequent production of affinity-matured antibodies does not always require TCR engagement. 36,37 We set out to characterize the sequence of these three β-WTA-reactive antibodies to better understand their evolution from germline sequences (Figure 7).…”

“…An important component of immune defenses against bacteria is a repertoire of germline “natural antibodies” that have affinity for non-protein bacterial epitopes such as carbohydrates. 16,17 These antibodies are produced in the absence of T-cell stimulation early in the course of infection, with the best-characterized Gram-positive responses against cell wall epitopes such as poly-N-acetylglucosamine (PNAG) and capsular polysaccharide (CP) teichoic acids from Staphylococcus species 18,19 and Streptococcus pneumoniae . 20 In addition, CPs are an important component of several bacterial vaccines, 21 and opsonizing antibodies targeting polysaccharides have been investigated as therapeutic agents for Burkholderia dolosa 22 and S. aureus .…”

A Hard(y) Look at B-1 Cell Development and Function

“…They showed that injection of α1-3 dextran permanently altered the repertoire of carbohydrate-reactive B cells when given within a short window after birth, but not later (summarized in (62)). This antigen is known to activate B-1 cells (63), and is expressed on Aspergillus fumigatus as well as house dust mites, While immunization did not change anti- α1-3 dextran serum IgM levels, it expanded the repertoire of polysaccharide-specific B cells and protected the mice from increased airway reactivity and signs of TH2-mediated airway disease (64).…”

Glycan Arrays: From Basic Biochemical Research to Bioanalytical and Biomedical Applications

“…Natural antibodies against carbohydrates are found in humans and other mammals. Their origin is a matter of debate, but exposure to microbial carbohydrates is believed to play a major role in their formation (123). Naturally acquired antiglycan antibodies vary Antibody analysis using glycan arrays for cancer research.…”