Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide
| Autor: | Hirotaka Ogata, Yoichiro Iwakura, Sachiko Akashi, Hidetoshi Yamasaki, Yoshinori Nagai, Kensuke Miyake, Katsuko Sudo, Rintaro Shimazu, Shin-Ichi Hayashi, Masao Kimoto |
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| Rok vydání: | 2002 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide Immunology Biology Lymphocyte Activation Biochemistry Microbiology chemistry.chemical_compound Mice Antigen Antigens CD medicine Animals Drug Interactions Receptor B cell CD86 Mice Knockout B-Lymphocytes Mice Inbred BALB C Antibodies Monoclonal Cell Biology Hematology Cell biology Mice Inbred C57BL medicine.anatomical_structure chemistry Antigens Surface TLR4 biology.protein lipids (amino acids peptides and proteins) Antibody Signal transduction Spleen |
| Zdroj: | Blood. 99(5) |
| ISSN: | 0006-4971 |
| Popis: | RP105 is a B-cell surface molecule that has been recently assigned as CD180. RP105 ligation with an antibody induces B-cell activation in humans and mice, leading to proliferation and up-regulation of a costimulatory molecule, B7.2/CD86. RP105 is associated with an extracellular molecule, MD-1. RP105/MD-1 has structural similarity to Toll-like receptor 4 (TLR4)/MD-2. TLR4 signals a membrane constituent of Gram-negative bacteria, lipopolysaccharide (LPS). MD-2 is indispensable for TLR4-dependent LPS responses because cells expressing TLR4/MD-2, but not TLR4 alone, respond to LPS. RP105 also has a role in LPS responses because B cells lacking RP105 show hyporesponsiveness to LPS. Little is known, however, regarding whether MD-1 is important for RP105-dependent LPS responses, as MD-2 is for TLR4. To address the issue, we developed mice lacking MD-1 and generated monoclonal antibodies (mAbs) to the protein. MD-1–null mice showed impairment in LPS-induced B-cell proliferation, antibody production, and B7.2/CD86 up-regulation. These phenotypes are similar to those of RP105-null mice. The similarity was attributed to the absence of cell surface RP105 on MD-1–null B cells. MD-1 is indispensable for cell surface expression of RP105. A role for MD-1 in LPS responses was further studied with anti–mouse MD-1 mAbs. In contrast to highly mitogenic anti-RP105 mAbs, the mAbs to MD-1 were not mitogenic but antagonistic on LPS-induced B-cell proliferation and on B7.2 up-regulation. Collectively, MD-1 is important for RP105 with respect to B-cell surface expression and LPS recognition and signaling. |
| Databáze: | OpenAIRE |
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