Langerhans cells promote early germinal center formation in response to Leishmania‐derived cutaneous antigens. Issue 10 (October 2014)

• Record Type: Journal Article
• Authors: Zimara, Nicole; Florian, Christian; Schmid, Maximilian; Malissen, Bernard; Kissenpfennig, Adrien; Männel, Daniela N.; Edinger, Matthias; Hutchinson, James A.; Hoffmann, Petra; Ritter, Uwe
• Is Part Of: European journal of immunology. Volume 44:Issue 10(2014:Oct.)
• Page Start: 2955
• Page End: 2967
• Publication Date: 2014-10
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201344263
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Efficient formation of early GCs depends on the close interaction between GC B cells and antigen‐primed CD4<sup>+</sup> follicular helper T cells (T<sub>FH</sub>). A tight and stable formation of T<sub>FH</sub>/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<sub>FH</sub>/B cell conjugates is crucial for B‐cell differentiation and class switch following infection with <italic>Leishmania major</italic> parasites. However, the subtype of DCs responsible for T<sub>FH</sub>‐cell priming against dermal antigens is thus far unknown. Utilizing a transgenic C57BL/6 mouse model designed to trigger the ablation of Langerin<sup>+</sup> DC subsets in vivo, we show that the functionality of T<sub>FH</sub>/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<sub>FH</sub>/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 <italic>Leishmania major</italic> 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.</p> </abstract>