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Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):1334-1339. doi: 10.1073/pnas.1715618115. Epub 2018 Jan 22.

Nonfollicular reactivation of bone marrow resident memory CD4 T cells in immune clusters of the bone marrow.

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Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, 10117 Berlin, Germany.
Osteoimmunology, DRFZ Berlin, 10117 Berlin, Germany.
Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, 10117 Berlin, Germany;


The bone marrow maintains memory CD4 T cells, which provide memory to systemic antigens. Here we demonstrate that memory CD4 T cells are reactivated by antigen in the bone marrow. In a secondary immune response, antigen-specific T cells of the bone marrow mobilize and aggregate in immune clusters together with MHC class II-expressing cells, mostly B lymphocytes. They proliferate vigorously and express effector cytokines, but they do not develop into follicular T-helper cells. Neither do the B lymphocytes develop into germinal center B cells in the bone marrow. Within 10 days, the immune clusters disappear again. Within 30 days, the expanded antigen-specific memory CD4 T cells return to memory niches and are maintained again individually as resting cells. Thus, in secondary immune responses in the bone marrow T-cell memory is amplified, while in germinal center reactions of secondary lymphoid organs humoral memory is adapted by affinity maturation.


bone marrow; immune clusters; reactivation; secondary immune reaction; tissue-resident CD4 memory T cells

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