CSF-1 receptor-mediated differentiation of a new type of monocytic cell with B cell-stimulating activity: its selective dependence on IL-34.
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.
3.Okayama University Graduate School of Natural Science and Technology, Tsushima-Naka 3-1-1, Kita-ku, Okayama 700-8530, Japan. magari@cc.okayama-u.ac.jp (M.M.) or hit2224@cc.okayama-u.ac.jp (H.O.).
Fumihiro
F
Yamane
Yumiko
Y
Nishikawa
Kazue
K
Matsui
Miki
M
Asakura
Eriko
E
Iwasaki
Koji
K
Watanabe
Hikaru
H
Tanimoto
Hiroki
H
Sano
Yuki
Y
Fujiwara
E Richard
ER
Stanley
Naoki
N
Kanayama
Neil A
NA
Mabbott
Masaki
M
Magari
Hitoshi
H
Ohmori
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D018920:Coculture Techniques; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D016130:Immunophenotyping; D007378:Interleukins / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D010586:Phagocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D007378:Interleukins; C552364:interleukin-34, mouse; D016186:Receptor, Macrophage Colony-Stimulating Factor
CD11b; follicular dendritic cells; mouse spleen