Staphylococcus aureus Cowan I-induced human immunoglobulin responses: Preferential IgM rheumatoid factor production and VH3 mRNA expression by protein A-binding B cells

Abstract

Protein A (PA), a cell wall component of SAC, activates human B cells by cross-linking the Fabs of membrane immunoglobulins. Recent data indicate that PA binds only to Fabs that use VH3 heavy chains, and thus it has been designated as a B-cell superantigen. We previously reported that Staphylococcus aureus Cowan I (SAC)-induced IgM rheumatoid factor (RF) by human PBMC was mediated by PA. Therefore, we sought to determine if SAC-induced IgMRF production was confined to PA-binding B cells and if these B cells were enriched for the expression of VH3 heavy chains. We observed that the elicitation of IgMRF in response to SAC was limited to a subset of B cells that bind PA and that this subset was enriched for VH3 mRNA expression. Taken together, these results suggest that IgMRFs produced in response to SAC are enriched for usage of VH3 heavy chains. Thus, this SAC-induced autoantibody response appears to represent a new B-cell superantigenic property of PA.

Unlike in Children with Allergic Asthma, IgE Transcripts from Preschool Children with Atopic Dermatitis Display Signs of Superantigen-Driven Activation

“…Other staphylococcal superantigens, however, favor usage of genes from the V H 3 family (27, 28). Kozlowski et al reported that IgM transcripts produced in response to S. aureus protein A are enriched for V H 3 H chains (29).…”

B-Cell Superantigens: Molecular and Cellular Implications

“…This correlation was later extended in studies of IgG and IgA Abs [30,31]. The restricted association with vH3 gene usage has now been confirmed by several other groups [16,17,, and there has not been a single reported example in which a non-V~3 Ab displayed comparable binding activity (see below).…”

Staphylococcal Protein A Binding to VH3Encoded Immunoglobulins

“…Hence, SPA binding is thought to occur outside of the classical antigen binding site and, thus, is considered a B-cell superantigen [30]. In support of this classification, SPA has been shown not only to preferentially bind to B cells expressing VH, encoded antibodies, SPA also delivers activation signals to stimulate the differentiation of these B cells and immunoglobulin production [19,23].…”

“…aureus Cowan I has been shown to stimulate IgM rheumatoid factor production by peripheral blood mononuclear cells of healthy people [55]. IgM R F production was limited to a subset of B cells which bound SPA and was enriched for expression of VHI encoded heavy chains [23]. Superantigens, therefore, have the potential of influencing the B cell repertoire, forming immune complexes which can activate, complement and induce the production of autoantibodies.…”

“…SPA binding, therefore, is considered a functional marker for v H 3 IgM [14,15,17,23,29,30]. SPA also binds in the Fab portion of murine immunoglobulins which are primarily encoded by members of the 5606 and S107 VH gene families [ 15,181. In both species, nucleotide sequencing indicates that a wide variety of D, JH, VL and JL gene segments are used [13-I 5,181.…”