The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/2/551/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 3, February 3, 1997 551-562

Articles

Viral Superantigen Drives Extrafollicular and Follicular B Cell Differentiation Leading to Virus-specific Antibody Production

Sanjiv A. Luther*, Adam Gulbranson-Judge§, Hans Acha-Orbea*,{ddagger}, and Ian C.M. MacLennan§

From the * Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland; the {ddagger} Institute of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland; and the § Department of Immunology, University of Birmingham Medical School, Birmingham, B15 2TT, United Kingdom

Mouse mammary tumor virus (MMTV[SW]) encodes a superantigen expressed by infected B cells. It evokes an antibody response specific for viral envelope protein, indicating selective activation of antigen-specific B cells. The response to MMTV(SW) in draining lymph nodes was compared with the response to haptenated chicken gamma globulin (NP-CGG) using flow cytometry and immunohistology. T cell priming occurs in both responses, with T cells proliferating in association with interdigitating dendritic cells in the T zone. T cell proliferation continues in the presence of B cells in the outer T zone, and B blasts then undergo exponential growth and differentiation into plasma cells in the medullary cords. Germinal centers develop in both responses, but those induced by MMTV(SW) appear later and are smaller. Most T cells activated in the T zone and germinal centers in the MMTV(SW) response are superantigen specific and these persist for weeks in lymph nodes draining the site MMTV(SW) injection; this contrasts with the selective loss of superantigen-specific T cells from other secondary lymphoid tissues. The results indicate that this viral superantigen, when expressed by professional antigen-presenting cells, drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production.

Address correspondence to Professor I.C.M. MacLennan, Department of Immunology, University of Birmingham, Birmingham, B15 2TT, United Kingdom.

The authors would like to thank H.R. MacDonald, who suggested this collaboration between the group studying MMTV in Lausanne and that in Birmingham, which works on the analysis of cellular interactions in vivo during antibody responses.

The work in Birmingham was supported by a Medical Research Council Programme grant to I.C.M. MacLennan; that in Lausanne was supported by grant number 31-42468.94 from the Swiss National Science Foundation to H. Acha-Orbea.

1Abbreviations used in this paper: IDC, interdigitating dendritic cells; MMTV, mouse mammary tumor virus; NP-CGG, haptenated chicken gamma globulin; PNA, peanut agglutinin; SAg, superantigen.


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