Novel Specialized Cell State and Spatial Compartments Within the Germinal Center

Overview

Journal Nat Immunol

Date 2020 Apr 29

PMID 32341509

Citations 43

Authors

Domenick E Kennedy

Michael K Okoreeh

Mark Maienschein-Cline

Junting Ai

Margaret Veselits

Kaitlin C McLean

Yogesh Dhungana

Hong Wang

Junmin Peng

Hongbo Chi

Malay Mandal

Marcus R Clark

Affiliations

Soon will be listed here.

Abstract

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.

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