| First Author | Pirgova G | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 22 | Pages | 12295-12305 |
| PubMed ID | 32424104 | Mgi Jnum | J:288614 |
| Mgi Id | MGI:6433548 | Doi | 10.1073/pnas.1921673117 |
| Citation | Pirgova G, et al. (2020) Marginal zone SIGN-R1(+) macrophages are essential for the maturation of germinal center B cells in the spleen. Proc Natl Acad Sci U S A 117(22):12295-12305 |
| abstractText | 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. |
