RESEARCH - Exclusion of natural autoantibody-producing B cells from IgG memory B cell compartment during T cell-dependent immune responses

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J Immunol. 2009 Jun 15;182(12):7634-43.

Exclusion of natural autoantibody-producing B cells from IgG memory B

cell compartment during T cell-dependent immune responses.

Matejuk A, Beardall M, Xu Y, Tian Q, D, Alabyev B, Mannoor K, Chen C.

Department of Pathology, University of land School of Medicine,

Baltimore, MD 21201, USA.

In healthy individuals, a substantial proportion of circulating Abs

exhibit polyreactivity and self-reactivity. These Abs are referred to

as natural autoantibodies (NAAs). As part of the innate immunity, NAAs

play an important role in eliminating pathogens. However, inherent to

their poly/autoreactivity is the potential for NAAs to differentiate

to high-affinity autoantibodies during an immune response. We recently

generated site-directed transgenic mice that express a prototypic NAA,

ppc1-5, which binds a variety of self- and non-self-Ags including DNA

and phosphocholine. We have shown previously that B cells expressing

the ppc1-5 NAA are positively selected during their primary

development. In this study, we demonstrate that following immunization

with the T-dependent Ag, phosphocholine conjugated to keyhole limpet

hemocyanin, ppc1-5 NAA B cells mounted a quick IgM Ab response and

entered germinal centers, but they failed to differentiate to

IgG-producing cells during late primary and memory responses.

Hybridomas and cDNA clones derived from the immunized mice included

many IgM NAA-producing cells, but IgG NAA clones were extremely rare.

Instead, many of the IgG B cells replaced their IgH transgene with an

endogenous V(H) gene and produced non-autoreactive Abs. These results

indicate that although NAA B cells are positively selected in the

preimmune repertoire and can participate in early IgM Ab response,

they are subjected to regulatory mechanisms that prevent them from

developing to high-affinity IgG autoantibody production. This would

explain, at least in part, why NAAs do not cause autoimmunity in most

individuals.

PMID: 19494287

http://www.ncbi.nlm.nih.gov/pubmed/19494287

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