TY - JOUR
T1 - CSF-1 receptor-mediated differentiation of a new type of monocytic cell with B cell-stimulating activity
T2 - Its selective dependence on IL-34
AU - Yamane, Fumihiro
AU - Nishikawa, Yumiko
AU - Matsui, Kazue
AU - Asakura, Miki
AU - Iwasaki, Eriko
AU - Watanabe, Koji
AU - Tanimoto, Hikaru
AU - Sano, Hiroki
AU - Fujiwara, Yuki
AU - Richard Stanley, E.
AU - Kanayama, Naoki
AU - Mabbott, Neil A.
AU - Magari, Masaki
AU - Ohmori, Hitoshi
PY - 2014/1
Y1 - 2014/1
N2 - With the use of a mouse FDC line, FL-Y, we have been analyzing roles for FDCs in controlling B cell fate in GCs. Beside these regulatory functions, we fortuitously found that FL-Y cells induced a new type of CD11b+ monocytic cells (F4/80+, Gr-1-, Ly6C-, I-A/E-/lo, CD11c-, CD115+, CXCR4+, CCR2+, CX3CR1-) when cultured with a Lin-c-kit+ population from mouse spleen cells. The developed CD11b+ cells shared a similar gene-expression profile to mononuclear phagocytes and were designated as FDMCs. Here, we describe characteristic immunological functions and the induction mechanism of FDMCs. Proliferation of anti-CD40 antibody-stimulated B cells was markedly accelerated in the presence of FDMCs. In addition, the FDMC-activated B cells efficiently acquired GC B cell-associated markers (Fas and GL-7). We observed an increase of FDMC-like cells in mice after immunization. On the other hand, FL-Y cells were found to produce CSF-1 as well as IL-34, both of which are known to induce development of macrophages and monocytes by binding to the common receptor, CSF-1R, expressed on the progenitors. However, we show that FL-Y-derived IL-34, but not CSF-1, was selectively responsible for FDMC generation using neutralizing antibodies and RNAi. We also confirmed that FDMC generation was strictly dependent on CSF-1R. To our knowledge, a CSF-1R-mediated differentiation process that is intrinsically specific for IL-34 has not been reported. Our results provide new insights into understanding the diversity of IL-34 and CSF-1 signaling pathways through CSF-1R.
AB - With the use of a mouse FDC line, FL-Y, we have been analyzing roles for FDCs in controlling B cell fate in GCs. Beside these regulatory functions, we fortuitously found that FL-Y cells induced a new type of CD11b+ monocytic cells (F4/80+, Gr-1-, Ly6C-, I-A/E-/lo, CD11c-, CD115+, CXCR4+, CCR2+, CX3CR1-) when cultured with a Lin-c-kit+ population from mouse spleen cells. The developed CD11b+ cells shared a similar gene-expression profile to mononuclear phagocytes and were designated as FDMCs. Here, we describe characteristic immunological functions and the induction mechanism of FDMCs. Proliferation of anti-CD40 antibody-stimulated B cells was markedly accelerated in the presence of FDMCs. In addition, the FDMC-activated B cells efficiently acquired GC B cell-associated markers (Fas and GL-7). We observed an increase of FDMC-like cells in mice after immunization. On the other hand, FL-Y cells were found to produce CSF-1 as well as IL-34, both of which are known to induce development of macrophages and monocytes by binding to the common receptor, CSF-1R, expressed on the progenitors. However, we show that FL-Y-derived IL-34, but not CSF-1, was selectively responsible for FDMC generation using neutralizing antibodies and RNAi. We also confirmed that FDMC generation was strictly dependent on CSF-1R. To our knowledge, a CSF-1R-mediated differentiation process that is intrinsically specific for IL-34 has not been reported. Our results provide new insights into understanding the diversity of IL-34 and CSF-1 signaling pathways through CSF-1R.
KW - CD11b
KW - Follicular dendritic cells
KW - Mouse spleen
UR - http://www.scopus.com/inward/record.url?scp=84897018686&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897018686&partnerID=8YFLogxK
U2 - 10.1189/jlb.0613311
DO - 10.1189/jlb.0613311
M3 - Article
C2 - 24052571
AN - SCOPUS:84897018686
SN - 0741-5400
VL - 95
SP - 19
EP - 31
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 1
ER -