Open AccessNovel specialized cell state and spatial compartments within the germinal center
Author(s) -
Domenick E. Kennedy,
Michael K. Okoreeh,
Mark MaienscheinCline,
Junting Ai,
Margaret Veselits,
Kaitlin C. McLean,
Yogesh Dhungana,
Hong Wang,
Junmin Peng,
Hongbo Chi,
Malay Mandal,
Marcus R. Clark
Publication year - 2020
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/s41590-020-0660-2
Subject(s) - somatic hypermutation , germinal center , biology , population , microbiology and biotechnology , somatic cell , genetics , b cell , antibody , gene , demography , sociology
Within germinal centers (GCs), complex and highly orchestrated molecular programs must balance proliferation, somatic hypermutation and selection to both provide effective humoral immunity and to protect against genomic instability and neoplastic transformation. In contrast to this complexity, GC B cells are canonically divided into two principal populations, dark zone (DZ) and light zone (LZ) cells. We now demonstrate that, following selection in the LZ, B cells migrated to specialized sites within the canonical DZ that contained tingible body macrophages and were sites of ongoing cell division. Proliferating DZ (DZp) cells then transited into the larger DZ to become differentiating DZ (DZd) cells before re-entering the LZ. Multidimensional analysis revealed distinct molecular programs in each population commensurate with observed compartmentalization of noncompatible functions. These data provide a new three-cell population model that both orders critical GC functions and reveals essential molecular programs of humoral adaptive immunity.