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Expression and Relationships of Seven Public Idiotypes of DNA-Binding Autoantibodies on Monoclonal Antibodies and Serum Immunoglobulins

Infection & Immunity Research Group, King's College London, London

C.T. Ravirajan

Infection & Immunity Research Group, King's College London, London

A. Morgan

Infection & Immunity Research Group, King's College London, London

A.J. Belcher

Infection & Immunity Research Group, King's College London, London

A.J. Henry

Infection & Immunity Research Group, King's College London, London

R.A. Lake

Infection & Immunity Research Group, King's College London, London

D.A. Smith

Infection & Immunity Research Group, King's College London, London

A.S. Hamblin

Department of Immunology, UMDS, St Thomas' Campus, London, UK

M. Hara

Institute of Rheumatology, Tokyo Women's Medical College, Tokyo, Japan

D. Adu

Renal Unit, Queen Elizabeth Hospital, Birmingham

C. Morland

Renal Unit, Queen Elizabeth Hospital, Birmingham

D.A. Isenberg

Bloomsbury Rheumatology Unit, The Department of Rheumatology Research, University College School of Medicine, London, UK

Many studies have shown that DNA-reactive autoantibodies share cross-reactive public idiotypes that are defined, usually, by single anti-idiotype reagents. Because anti-idiotype antibodies or antisera will be limited in their ability to detect all the idiotopes of a particular antibody, their use will tend to underestimate the full extent of idiotype sharing between different antibodies. In order to define more comprehensively the extent of idiotype sharing in DNA autoantibodies, a panel of DNA-binding monoclonal autoantibodies from lupus mice was examined with a range of anti-idiotype antisera prepared in rabbits (five sera), guinea pigs (four sera) and a sheep. Each idiotype was detected on more antibodies than its original reference monoclonal antibody, and idiotopes of each were also present on serum immunoglobulins from lupus mice. Of 23 monoclonal antibodies 65% reacted with one or more of the anti-idiotype reagents. On these criteria, all the idiotypes were public; none was private in its expression.

In about half the cases the idiotypes were located in or near the antigen-binding sites of the antibodies, but a direct relationship to specificity was not obvious except in the case of Id.228 present on antibodies with a relatively high affinity for single-stranded DNA. In other cases there was no obvious relationship between idiotype and specificity. Antibodies from the same mouse did not each express the same array of idiotopes. None of the idiotypes was restricted to either (NZB x NZW)F₁ or MRL/Mp-lpr/lpr mice, but there were differences between the strains. In the former, the expression of idiotype Id.88 notably decreased with age, whereas it rose with age in mice of the latter strain. The extent of sharing of the idiotypes of these DNA antibodies indicates that the great majority of the antibodies are related to each other idiotypically. From these studies, it is clear that the definition of idiotype sharing can be achieved comprehensively only if antibodies against many idiotopes are used.

Key Words: DNA antibody • Idiotype • Monoclonal antibody • Systemic lupus erythematosus

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