The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/9/851/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 6, September 20, 1999 851-860

A Member of the Dendritic Cell Family That Enters B Cell Follicles and Stimulates Primary Antibody Responses Identified by a Mannose Receptor Fusion Protein

Claude Berneya, Suzanne Herrena, Christine A. Powera, Siamon Gordonb, Luisa Martinez-Pomaresb, and Marie H. Kosco-Vilboisa
a Serono Pharmaceutical Research Institute, CH-1228 Geneva, Switzerland
b Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom

Correspondence to: Marie H. Kosco-Vilbois, Serono Pharmaceutical Research Institute, 14, chemin des Aulx, CH-1228 Geneva, Switzerland. Tel:41-22-706-9708 Fax:41-22-794-6965 E-mail:marie.kosco-vilbois{at}serono.com.

Dendritic cells (DCs) are known to activate naive T cells to become effective helper cells. In addition, recent evidence suggests that DCs may influence naive B cells during the initial priming of antibody responses. In this study, using three-color confocal microscopy and three-dimensional immunohistograms, we have observed that in the first few days after a primary immunization, cells with dendritic morphology progressively localize within primary B cell follicles. These cells were identified by their ability to bind a fusion protein consisting of the terminal cysteine-rich portion of the mouse mannose receptor and the Fc portion of human immunoglobulin (Ig)G1 (CR-Fc). In situ, these CR-Fc binding cells express major histocompatibility complex class II, sialoadhesin, and CD11c and are negative for other markers identifying the myeloid DC lineage, such as (CD11b), macrophages (F4/80), follicular DCs (FDC-M2), B cells (B220), and T cells (CD4). Using CR-Fc binding capacity and flow cytometry, the cells were purified from the draining lymph nodes of mice 24 h after immunization. When injected into naive mice, these cells were able to prime T cells as well as induce production of antigen-specific IgM and IgG1. Furthermore, they produced significantly more of the lymphocyte chemoattractant, macrophage inflammatory protein (MIP)-1{alpha}, than isolated interdigitating cells. Taken together, these results provide evidence that a subset of DCs enters primary follicles, armed with the capacity to attract and provide antigenic stimulation for T and B lymphocytes.

Key Words: dendritic cells, mannose receptor, antibody production, antigen presentation, chemokines


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