| 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
|
| Resource |
| Mice |
RBRC04395 |
