Macrophage migration inhibitory factor induces B cell survival by activation of a CD74-CD44 receptor complex.
Macrophage migration inhibitory factor (MIF) is an upstream activator of innate immunity that regulates subsequent adaptive responses. It was previously shown that in macrophages, MIF binds to a complex of CD74 and CD44, resulting in initiation of a signaling pathway. In the current study, we investigated the role of MIF in B cell survival. We show that in B lymphocytes, MIF initiates a signaling cascade that involves Syk and Akt, leading to NF-kappaB activation, proliferation, and survival in a CD74- and CD44-dependent manner. Thus, MIF regulates the adaptive immune response by maintaining the mature B cell population.
Department of Immunology, the Weizmann Institute of Science, Rehovot 76100, Israel.
Yael
Y
Gore
Diana
D
Starlets
Nitsan
N
Maharshak
Shirly
S
Becker-Herman
Utako
U
Kaneyuki
Lin
L
Leng
Richard
R
Bucala
Idit
I
Shachar
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D001483:Base Sequence; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018960:Hyaluronan Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D019746:Intramolecular Oxidoreductases / Q000378:metabolism / Q000494:pharmacology*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046912:Multiprotein Complexes; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D000944:Antigens, Differentiation, B-Lymphocyte; C476399:Cd44 protein, mouse; D017931:DNA Primers; D000949:Histocompatibility Antigens Class II; D018960:Hyaluronan Receptors; D008263:Macrophage Migration-Inhibitory Factors; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; C045084:invariant chain; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse