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Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity.
Dosenovic, Pia; Kara, Ervin E; Pettersson, Anna-Klara; McGuire, Andrew T; Gray, Matthew; Hartweger, Harald; Thientosapol, Eddy S; Stamatatos, Leonidas; Nussenzweig, Michel C.
Afiliação
  • Dosenovic P; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065-6322.
  • Kara EE; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065-6322.
  • Pettersson AK; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065-6322.
  • McGuire AT; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
  • Gray M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
  • Hartweger H; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065-6322.
  • Thientosapol ES; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065-6322.
  • Stamatatos L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
  • Nussenzweig MC; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065-6322; nussen@rockefeller.edu.
Proc Natl Acad Sci U S A ; 115(18): 4743-4748, 2018 05 01.
Article em En | MEDLINE | ID: mdl-29666227
ABSTRACT
The discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts to develop an antibody-based HIV-1 vaccine. Antibody cloning from single cells revealed that nearly all bNAbs show unusual features that could help explain why it has not been possible to elicit them by traditional vaccination and instead would require a sequence of different immunogens. This idea is supported by experiments with genetically modified immunoglobulin (Ig) knock-in mice. Sequential immunization with a series of specifically designed immunogens was required to shepherd the development of bNAbs. However, knock-in mice contain superphysiologic numbers of bNAb precursor-expressing B cells, and therefore how these results can be translated to a more physiologic setting remains to be determined. Here we make use of adoptive transfer experiments using knock-in B cells that carry a synthetic intermediate in the pathway to anti-HIV-1 bNAb development to examine how the relationship between B cell receptor affinity and precursor frequency affects germinal center (GC) B cell recruitment and clonal expansion. Immunization with soluble HIV-1 antigens can recruit bNAb precursor B cells to the GC when there are as few as 10 such cells per mouse. However, at low precursor frequencies, the extent of clonal expansion is directly proportional to the affinity of the antigen for the B cell receptor, and recruitment to GCs is variable and dependent on recirculation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Anticorpos Anti-HIV / Antígenos HIV / HIV-1 / Células Precursoras de Linfócitos B / Anticorpos Neutralizantes / Afinidade de Anticorpos Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Anticorpos Anti-HIV / Antígenos HIV / HIV-1 / Células Precursoras de Linfócitos B / Anticorpos Neutralizantes / Afinidade de Anticorpos Limite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2018 Tipo de documento: Article