Zimara, Nicole and Florian, Christian and Schmid, Maximilian and Malissen, Bernard and Kissenpfennig, Adrien and Maennel, Daniela N. and Edinger, Matthias and Hutchinson, James A. and Hoffmann, Petra and Ritter, Uwe (2014) Langerhans cells promote early germinal center formation in response to Leishmania-derived cutaneous antigens. EUROPEAN JOURNAL OF IMMUNOLOGY, 44 (10). pp. 2955-2967. ISSN 0014-2980, 1521-4141
Full text not available from this repository. (Request a copy)Abstract
Efficient formation of early GCs depends on the close interaction between GC B cells and antigen-primed CD4(+) follicular helper T cells (T-FH). A tight and stable formation of T-FH/B cell conjugates is required for cytokine-driven immunoglobulin class switching and somatic hypermutation of GC B cells. Recently, it has been shown that the formation of T-FH/B cell conjugates is crucial for B-cell differentiation and class switch following infection with Leishmania major parasites. However, the subtype of DCs responsible for T-FH-cell priming against dermal antigens is thus far unknown. Utilizing a transgenic C57BL/6 mouse model designed to trigger the ablation of Langerin(+) DC subsets in vivo, we show that the functionality of T-FH/B cell conjugates is disturbed after depletion of Langerhans cells (LCs): LC-depleted mice show a reduction in somatic hypermutation in B cells isolated from T-FH/B cell conjugates and markedly reduced GC reactions within skin-draining lymph nodes. In conclusion, this study reveals an indispensable role for LCs in promoting GC B-cell differentiation following cutaneous infection with Leishmania major parasites. We propose that LCs are key regulators of GC formation and therefore have broader implications for the development of allergies and autoimmunity as well as for future vaccination strategies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CD4 T-CELLS; LANGERIN(+) DENDRITIC CELLS; KEYHOLE LIMPET HEMOCYANIN; FOLLICULAR-HELPER-CELLS; B-CELLS; LYMPH-NODE; IN-VIVO; DIFFERENTIATION; BCL-6; ACTIVATION; B cells; Follicular helper; Germinal center reaction; Langerhans cells; Leishmania major; T cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Aug 2019 13:18 |
| Last Modified: | 12 Aug 2019 13:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9407 |
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