RRC ID 59230
Author Pirgova G, Chauveau A, MacLean AJ, Cyster JG, Arnon TI.
Title Marginal zone SIGN-R1+ macrophages are essential for the maturation of germinal center B cells in the spleen.
Journal Proc Natl Acad Sci U S A
Abstract The mechanisms that regulate germinal center (GC) B cell responses in the spleen are not fully understood. Here we use a combination of pharmacologic and genetic approaches to delete SIGN-R1+ marginal zone (MZ) macrophages and reveal their specific contribution to the regulation of humoral immunity in the spleen. We find that while SIGN-R1+ macrophages were not essential for initial activation of B cells, they were required for maturation of the response and development of GC B cells. These defects could be corrected when follicular helper T (Tfh) cells were induced before macrophage ablation or when Tfh responses were enhanced. Moreover, we show that in the absence of SIGN-R1+ macrophages, DCIR2+ dendritic cells (DCs), which play a key role in priming Tfh responses, were unable to cluster to the interfollicular regions of the spleen and were instead displaced to the MZ. Restoring SIGN-R1+ macrophages to the spleen corrected positioning of DCIR2+ DCs and rescued the GC B cell response. Our study reveals a previously unappreciated role for SIGN-R1+ macrophages in regulation of the GC reaction and highlights the functional specification of macrophage subsets in the MZ compartment.
Volume 117(22)
Pages 12295-12305
Published 2020-6-2
DOI 10.1073/pnas.1921673117
PII 1921673117
PMID 32424104
PMC PMC7275705
MeSH Animals B-Lymphocytes / immunology* Cell Adhesion Molecules / genetics Cell Adhesion Molecules / immunology* Germinal Center / immunology* Lectins, C-Type / genetics Lectins, C-Type / immunology* Lymphocyte Activation Macrophages / immunology* Mice, Inbred C57BL Mice, Knockout Receptors, Cell Surface / genetics Receptors, Cell Surface / immunology* Spleen / immunology* T-Lymphocytes, Helper-Inducer
IF 9.412
Times Cited 0
Mice RBRC04395