血清记忆(Serologic memory)是长期免疫效能的一个重要因素,但我们对由被HIV等重要人类病原体感染的人体中记忆B细胞所产生的抗体却几乎不了解。为了对HIV的记忆抗体反应进行研究,Scheid等人从来自具有高血清值的广谱中和抗体的6个HIV感染者的HIV-特异性记忆B细胞中克隆出了超过500个抗体。这些患者体内B细胞对HIV的记忆反应由多达50个独立的、扩展的B-克隆组成,这些B-克隆表达一组针对不同病毒表位(抗原决定部位)的不同抗体,其中几个对于广谱HIV中和及有效免疫可能有重要作用。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 458, 636-640 (2 April 2009) | doi:10.1038/nature07930
Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals
Johannes F. Scheid1,6, Hugo Mouquet1, Niklas Feldhahn1, Michael S. Seaman7, Klara Velinzon1, John Pietzsch1,8, Rene G. Ott2, Robert M. Anthony2, Henry Zebroski3, Arlene Hurley4, Adhuna Phogat9, Bimal Chakrabarti9, Yuxing Li9, Mark Connors10, Florencia Pereyra11, Bruce D. Walker11, Hedda Wardemann12, David Ho13, Richard T. Wyatt9, John R. Mascola9, Jeffrey V. Ravetch2 & Michel C. Nussenzweig1,5
1 Laboratory of Molecular Immunology,
2 Laboratory of Molecular Genetics and Immunology,
3 Proteomics Resource Center,
4 Rockefeller University Hospital, and,
5 Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA
6 Charite Universitaetsmedizin, D-10117 Berlin, Germany
7 Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
8 Institute of Chemistry and Biochemistry, Freie Universit?t Berlin, D-14195 Berlin, Germany
9 Vaccine Research Center, and,
10 Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland 20892, USA
11 Partners AIDS Research Center, Mass General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
12 Max Planck Institute for Infection Biology, D-10117 Berlin, Germany
13 Aaron Diamond Aids Research Center; New York, New York 10065, USA
Antibodies to conserved epitopes on the human immunodeficiency virus (HIV) surface protein gp140 can protect against infection in non-human primates, and some infected individuals show high titres of broadly neutralizing immunoglobulin (Ig)G antibodies in their serum. However, little is known about the specificity and activity of these antibodies1, 2, 3. To characterize the memory antibody responses to HIV, we cloned 502 antibodies from HIV envelope-binding memory B cells from six HIV-infected patients with broadly neutralizing antibodies and low to intermediate viral loads. We show that in these patients, the B-cell memory response to gp140 is composed of up to 50 independent clones expressing high affinity neutralizing antibodies to the gp120 variable loops, the CD4-binding site, the co-receptor-binding site, and to a new neutralizing epitope that is in the same region of gp120 as the CD4-binding site. Thus, the IgG memory B-cell compartment in the selected group of patients with broad serum neutralizing activity to HIV is comprised of multiple clonal responses with neutralizing activity directed against several epitopes on gp120.