The Journal of Immunology, Vol 157, Issue 7 2976-2981, Copyright © 1996 by American Association of Immunologists

ARTICLES

Differential binding avidities of human IgM for staphylococcal protein A derive from specific germ-line VH3 gene usage

M Hakoda, N Kamatani, S Hayashimoto-Kurumada, GJ Silverman, H Yamanaka, C Terai and S Kashiwazaki
Institute of Rheumatology, Tokyo Women's Medical College, Japan.

Human IgM that express the variable region genes of the VH3 family bind staphylococcal protein A (SPA). We previously reported that the SPA- binding IgM can be divided into two groups based on the differential binding avidities for solid-phase SPA. To study the molecular basis for these differences, we cloned B cells from human blood by EBV transformation. The nucleotide sequences of the expressed Ig heavy chain genes were determined on 20 B cell clones that produce SPA- binding IgM. The germ-line VH3 gene usage in IgM with high avidities for SPA were distinct from the germ-line VH3 genes used in IgM with low avidities for SPA. There was no correlation in the usage of D or JH genes or in the usage of light chains in IgM according to the SPA binding avidity. These results suggest that the differential binding avidities for SPA are at least partly due to specific germ-line VH3 gene usage. An investigation of direct binding of SPA to the synthetic peptides corresponding to the portions of the variable regions of SPA- binding and non-SPA-binding IgM showed that the peptides corresponding to the VH3 family specific framework region 3 sequences had significant SPA binding capacities, while the peptides corresponding to the other subdomains and those corresponding to framework region 3 of the reported VH3 sequences from non-SPA-binding IgM showed little or no binding. It is of interest that the Ig-framework region 3 subdomain corresponds to the fourth hypervariable region, which in the TCR-beta chain has been implicated as a critical site for T cell superantigen binding.

This article has been cited by other articles:

				J Voswinkel, A Mueller, J A Kraemer, P Lamprecht, K Herlyn, K Holl-Ulrich, A C Feller, S Pitann, A Gause, and W L Gross B lymphocyte maturation in Wegener's granulomatosis: a comparative analysis of VH genes from endonasal lesions Ann Rheum Dis, July 1, 2006; 65(7): 859 - 864. [Abstract] [Full Text] [PDF]

				M. Tsuiji, S. Yurasov, K. Velinzon, S. Thomas, M. C. Nussenzweig, and H. Wardemann A checkpoint for autoreactivity in human IgM+ memory B cell development J. Exp. Med., February 21, 2006; 203(2): 393 - 400. [Abstract] [Full Text] [PDF]

				M. Graille, E. A. Stura, A. L. Corper, B. J. Sutton, M. J. Taussig, J.-B. Charbonnier, and G. J. Silverman Crystal structure of a Staphylococcus aureus protein A domain complexed with the Fab fragment of a human IgM antibody: Structural basis for recognition of B-cell receptors and superantigen activity PNAS, May 9, 2000; 97(10): 5399 - 5404. [Abstract] [Full Text] [PDF]

				M. Leonetti, J. Galon, R. Thai, C. Sautes-Fridman, G. Moine, and A. Menez Presentation of Antigen in Immune Complexes Is Boosted by Soluble Bacterial Immunoglobulin Binding Proteins J. Exp. Med., April 19, 1999; 189(8): 1217 - 1228. [Abstract] [Full Text] [PDF]

				S. Karray, L. Juompan, R. C. Maroun, D. Isenberg, G. J. Silverman, and M. Zouali Structural Basis of the gp120 Superantigen-Binding Site on Human Immunoglobulins J. Immunol., December 15, 1998; 161(12): 6681 - 6688. [Abstract] [Full Text] [PDF]

				M. Hakoda, N. Kamatani, A. Taniguchi, H. Ueda, H. Yamanaka, C. Terai, and S. Kashiwazaki Generation and molecular characterisation of monoclonal IgG4 rheumatoid factor from a patient with rheumatoid arthritis Ann Rheum Dis, January 1, 1997; 56(1): 74 - 77. [Abstract] [Full Text]