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Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2019
- Publisher :
- Rockefeller University Press, 2019.
-
Abstract
- An anti-idiotype recognizing the germline version of a broadly neutralizing antibody was utilized to identify human B cells expressing similar germline antibodies and was converted to an immunogen to stimulate transgenic murine B cells in vivo despite the presence of anergy.<br />Many tested vaccines fail to provide protection against disease despite the induction of antibodies that bind the pathogen of interest. In light of this, there is much interest in rationally designed subunit vaccines that direct the antibody response to protective epitopes. Here, we produced a panel of anti-idiotype antibodies able to specifically recognize the inferred germline version of the human immunodeficiency virus 1 (HIV-1) broadly neutralizing antibody b12 (iglb12). We determined the crystal structure of two anti-idiotypes in complex with iglb12 and used these anti-idiotypes to identify rare naive human B cells expressing B cell receptors with similarity to iglb12. Immunization with a multimerized version of this anti-idiotype induced the proliferation of transgenic murine B cells expressing the iglb12 heavy chain in vivo, despite the presence of deletion and anergy within this population. Together, our data indicate that anti-idiotypes are a valuable tool for the study and induction of potentially protective antibodies.
- Subjects :
- Adult
Male
0301 basic medicine
Precursor Cells, B-Lymphoid
Immunology
HIV Infections
Mice, Transgenic
HIV Antibodies
Antibodies, Neutralizing
Article
Antibodies, Anti-Idiotypic
3. Good health
Mice
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
HIV-1
Animals
Humans
Immunology and Allergy
Female
Research Articles
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 216
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....a4094229ea2bea1c4dab654c744920f3