B cells and professional APCs recruit regulatory T cells via CCL4

Abstract

Using gene expression profiling, we show here that activation of B cells and professional antigen-presenting cells (APCs) induces the expression of common chemokines. Among these, CCL4 was the most potent chemoattractant of a CD4+CD25+ T cell population, which is a characteristic phenotype of regulatory T cells. Depletion of either regulatory T cells or CCL4 resulted in a deregulated humoral response, which culminated in the production of autoantibodies. This suggested that the recruitment of regulatory T cells to B cells and APCs by CCL4 plays a central role in the normal initiation of T cell and humoral responses, and failure to do this leads to autoimmune activation.

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Figure 1: Chemokine expression profiles of primary B cells, DCs and macrophages before and after stimulation (a–c)
Figure 2: FACS analysis of the migration of CD25+ cell from the spleens of unimmunized mice.
Figure 3: CCL4 attracts regulatory T cells.
Figure 4: Accelerated GC formation upon reconstitution of nu/nu mice with CD25-depleted T cells or injection of neutralizing anti-CCL4.
Figure 5: The effect of regulatory T cells on B cell proliferation and blasting.
Figure 6: Anti-CCL4–treated mice developed IgG autoantibodies.

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Acknowledgements

We thank D. Fearon for his support and critical reading of the manuscript; K. J. Patel, M. S. Neuberger and C. Rada for helpful discussions; T. Langford and her team for animal handling; and A. Johnson for assistance with cell sorting.

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Correspondence to Alexander G. Betz.

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Bystry, R., Aluvihare, V., Welch, K. et al. B cells and professional APCs recruit regulatory T cells via CCL4. Nat Immunol 2, 1126–1132 (2001). https://doi.org/10.1038/ni735

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