Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling.
We have identified the lymphocyte semaphorin CD100/Sema4D as a CD40-inducible molecule by subtractive cDNA cloning. CD100 stimulation significantly enhanced the effects of CD40 on B cell responses. Administration of soluble CD100 markedly accelerated in vivo antigen-specific antibody responses. CD100 receptors with different binding affinities were detected on renal tubular cells (K(d) = approximately 1 x 10(-9)M) and lymphocytes (K(d) = approximately 3 x 10(-7)M). Expression cloning revealed that the CD100 receptor on lymphocytes is CD72, a negative regulator of B cell responsiveness. CD72 thus represents a novel class of semaphorin receptors. CD100 stimulation induced tyrosine dephosphorylation of CD72 and dissociation of SHP-1 from CD72. Our findings indicate that CD100 plays a critical role in immune responses by the novel mechanism of turning off negative signaling by CD72.
Kumanogoh
A
A
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita Osaka 565-0871, Japan.
Watanabe
C
C
Lee
I
I
Wang
X
X
Shi
W
W
Araki
H
H
Hirata
H
H
Iwahori
K
K
Uchida
J
J
Yasui
T
T
Matsumoto
M
M
Yoshida
K
K
Yakura
H
H
Pan
C
C
Parnes
J R
JR
Kikutani
H
H
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D008562:Membrane Glycoproteins / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D039961:Semaphorins; D015398:Signal Transduction / Q000276:immunology*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C093224:CD100 antigen; C064228:CD72 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D039961:Semaphorins