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Kai-Michael Toellner^*, Sanjiv A. Luther^,, Daniel M.-Y. Sze^*, Richard K.-W. Choy^*, Dale R. Taylor^*, Ian C.M. MacLennan^*, and Hans Acha-Orbea^,

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

The respective production of specific immunoglobulin (Ig)G2a or IgG1 within 5 d of primary immunization with Swiss type mouse mammary tumor virus [MMTV(SW)] or haptenated protein provides a model for the development of T helper 1 (Th1) and Th2 responses. The antibody-producing cells arise from cognate T cell B cell interaction, revealed by the respective induction of C2a and C1 switch transcript production, on the third day after immunization. T cell proliferation and upregulation of mRNA for interferon in response to MMTV(SW) and interleukin 4 in response to haptenated protein also starts during this day. It follows that there is minimal delay in these responses between T cell priming and the onset of cognate interaction between T and B cells leading to class switching and exponential growth. The Th1 or Th2 profile is at least partially established at the time of the first cognate T cell interaction with B cells in the T zone.

The addition of killed Bordetella pertussis to the hapten–protein induces nonhapten-specific IgG2a and IgG1 plasma cells, whereas the anti-hapten response continues to be IgG1 dominated. This indicates that a Th2 response to hapten–protein can proceed in a node where there is substantial Th1 activity.

¹ Abbreviations used in this paper: BrdU, 5-bromo-2'-deoxyuridine; CGG, chicken globulin; MMTV(SW), Swiss type mouse mammary tumor virus; NP, (4-hydroxy-3-nitrophenyl)acetyl.

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. S. A. Luther was funded by the Roche Research Foundation and Emma Muschamp Foundation.

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