Rhesus macaque Bcl-6/Bcl-xL B cell immortalization: Discovery of HIV-1 neutralizing antibodies from lymph node

被引：1

作者：

Samsel, Jakob ^{[1
,2
,7
]}

Boswell, Kristin L. ^{[1
]}

Watkins, Timothy ^{[1
]}

Ambrozak, David R. ^{[1
]}

Mason, Rosemarie ^{[3
,4
]}

Yamamoto, Takuya ^{[1
]}

Ko, Sungyoul ^{[3
,8
,9
]}

Yang, Yongping ^{[5
]}

Zhou, Tongqing ^{[5
]}

Doria-Rose, Nicole A. ^{[4
]}

Foulds, Kathryn E. ^{[6
]}

Roederer, Mario ^{[3
,5
]}

Mascola, John R. ^{[4
]}

Kwong, Peter D. ^{[5
]}

Gama, Lucio ^{[1
]}

Koup, Richard A. ^{[1
]}

机构：

[1] NIAID, NIH, Vaccine Res Ctr VRC, Immunol Lab, Bethesda, MD USA

[2] George Washington Univ, Inst Biomed Sci, Washington, DC USA

[3] VRC, ImmunoTechnol Sect, Bethesda, MD USA

[4] VRC, Humoral Immunol Sect, Bethesda, MD USA

[5] VRC, Struct Biol Sect, Bethesda, MD USA

[6] VRC, Nonhuman Primate Immunogen Core, Bethesda, MD USA

[7] NIHBC, 40 VRC BG RM 3612,40 CONVENT DR, Bethesda, MD 20892 USA

[8] Catholic Univ Korea, ILAb Co Ltd, Bucheon Si 14662, Gyeonggi Do, South Korea

[9] Catholic Univ Korea, Coll Pharm, Bucheon Si 14662, Gyeonggi Do, South Korea

来源：

JOURNAL OF IMMUNOLOGICAL METHODS | 2023年 / 516卷

基金：

美国国家卫生研究院;

关键词：

Antibody discovery; B cell immortalization; HIV; Vaccination; Rhesus macaque; MONOCLONAL-ANTIBODIES; GENERATION; EXPRESSION; FAMILY;

D O I：

10.1016/j.jim.2023.113445

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Many HIV-1 vaccines are designed to elicit neutralizing antibodies, and pre-clinical testing is often carried out in rhesus macaques (RMs). We have therefore adapted a method of B cell immortalization for use with RM B cells. In this system, RM B cells are activated with CD40 ligand and RM IL-21 before transduction with a retroviral vector encoding Bcl-6, Bcl-xL, and green fluorescent protein. Importantly, RM B cells from lymph nodes are more effectively immortalized by this method than B cells from PBMC, a difference not seen in humans. We suggest the discrepancy between these two tissues is due to increased expression of CD40 on RM lymph node B cells. Immortalized RM B cells expand long-term, undergo minimal somatic hypermutation, express surface B cell receptor, and secrete antibodies into culture. This allows for the identification of cells based on antigen specificity and/or functional assays. Here, we show the characterization of this system and its application for the isolation of HIV-1 neutralizing antibodies from a SHIV.CH505-infected animal, both with and without antigen probe. Taken together, we show that Bcl-6/xL immortalization is a valuable and flexible tool for antibody discovery in RMs, but with important distinctions from application of the system in human cells.

引用

页数：8

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