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Volume 33 Issue 6
December 2018

    Li Yuan, Wen-Jiang Chen, Jia-Ye Wang, Yan Li, Dan Tian, Ming-Xia Wang, Hao-Tong Yu, Ying-Chu Xu, Di Li, Min Zhuang and Hong Ling. Divergent Primary Immune Responses Induced by Human Immunodeficiency Virus-1 gp120 and Hepatitis B Surface Antigen Determine Antibody Recall Responses[J]. Virologica Sinica, 2018, 33(6): 502-514. doi: 10.1007/s12250-018-0074-6
    Citation: Li Yuan, Wen-Jiang Chen, Jia-Ye Wang, Yan Li, Dan Tian, Ming-Xia Wang, Hao-Tong Yu, Ying-Chu Xu, Di Li, Min Zhuang, Hong Ling. Divergent Primary Immune Responses Induced by Human Immunodeficiency Virus-1 gp120 and Hepatitis B Surface Antigen Determine Antibody Recall Responses .VIROLOGICA SINICA, 2018, 33(6) : 502-514.  http://dx.doi.org/10.1007/s12250-018-0074-6
    shu

    人类免疫缺陷病毒-1 gp120和乙肝表面抗原诱导的初级免疫应答差异决定了抗体回忆反应不同

    • 1.

      哈尔滨医科大学微生物学教研室

    • 2.

      黑龙江省感染与免疫重点实验室，黑龙江省普通高校病原生物学重点实验

    • 3.

      哈尔滨医科大学伍连德研究所

    • 4.

      哈尔滨医科大学免疫学教研室

    • 通讯作者： 凌虹, lingh@ems.hrbmu.edu.cn, ORCID: http://orcid.org/0000-0002-1886-1242
    • 收稿日期： 2018-09-09
      录用日期： 2018-11-07
      出版日期： 2018-12-19
    • 开发一种1型人类免疫缺陷病毒 (HIV-1)包膜糖蛋白(Env)相关并且能免疫诱导产生有效的抗感染保护抗体的疫苗是一项巨大的挑战。最近，我们比较了HIV-1 Env gp120和乙肝病毒表面抗原(HBsAg)的抗体产生模式，以了解如何提高基于Env的免疫原的保护效力。我们前期的研究表明HIV Env和HBsAg表现出不同的抗体诱导机制，并且T细胞在再次免疫应答中起着重要作用。本研究中，为阐明初级免疫反应在免疫记忆反应形成和抗体产生中的作用，我们用HIV-1 Env gp120和HBsAg抗原免疫C57BL/6小鼠，检测免疫小鼠初次免疫和加强免疫后滤泡辅助性T细胞(Tfh)和生发中心(GCs)的发育，以及免疫的记忆反应形成。我们发现在引流淋巴结中，与HBsAg相比，gp120免疫诱导产生更多Tfh细胞和细胞程序性死亡(PD) 1+ T细胞，B细胞表面表达更多的主要组织相容性复合体II分子，而活化B细胞水平相当，但HBsAg免疫诱导较弱的GC反应和记忆B细胞，伴随着更慢的抗体回忆反应和更弱的免疫记忆反应。以上结果提示，在初级免疫反应中诱导产生更多PD-1+ T细胞，可能是HIV-1 Env引起的抗体回忆反应迟缓的主要原因。

    Divergent Primary Immune Responses Induced by Human Immunodeficiency Virus-1 gp120 and Hepatitis B Surface Antigen Determine Antibody Recall Responses

    • 1.

      Department of Microbiology, Harbin Medical University, Harbin 150081, China

    • 2.

      Heilongjiang Provincial Key Laboratory of Infection and Immunity, Key Laboratory of Pathogen Biology, Harbin 150081, China

    • 3.

      Wu Lien-Teh Institute, Harbin Medical University, Harbin 150081, China

    • 4.

      Department of Immunology, Harbin Medical University, Harbin 150081, China

    • Corresponding author: Hong Ling, lingh@ems.hrbmu.edu.cn
    • ORCID: http://orcid.org/0000-0002-1886-1242
    • Received Date: 09 September 2018
      Accepted Date: 07 November 2018
      Published Date: 19 December 2018
    • The development of a vaccine based on human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the antibody production patterns of HIV-1 Env gp120 and hepatitis B virus surface antigen (HBsAg) to provide insights into how we may improve the protective efficacy of Env-based immunogens. Our previous study showed that HIV Env and HBsAg display different mechanisms of antibody elicitation and that T cells facilitate the responses to repeated immunizations. Here, to elucidate the detailed roles of primary immunization in immune memory response formation and antibody production, we immunized C57BL/6 mice with each antigen and evaluated the development of T follicular helper (Tfh) cells, germinal centers, and the memory responses involved in prime and boost immunizations. We found that after prime immunization, compared with HBsAg, gp120 induced higher frequencies of Tfh cells and programmed death (PD)-1+ T cells, greater major histocompatibility complex Ⅱ expression on B cells, comparable activated B cells, but weaker germinal center (GC) reactions and memory B cell responses in the draining lymph nodes, accompanied by slower antibody recall responses and poor immune memory responses. The above results suggested that more PD-1+ T cells arising in primary immunization may serve as major contributors to the slow antibody recall response elicited by HIV-1 Env.
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      Divergent Primary Immune Responses Induced by Human Immunodeficiency Virus-1 gp120 and Hepatitis B Surface Antigen Determine Antibody Recall Responses

        Corresponding author: Hong Ling, lingh@ems.hrbmu.edu.cn
      • 1. Department of Microbiology, Harbin Medical University, Harbin 150081, China
      • 2. Heilongjiang Provincial Key Laboratory of Infection and Immunity, Key Laboratory of Pathogen Biology, Harbin 150081, China
      • 3. Wu Lien-Teh Institute, Harbin Medical University, Harbin 150081, China
      • 4. Department of Immunology, Harbin Medical University, Harbin 150081, China
      • Received Date: 09 September 2018
      • Accepted Date: 07 November 2018
      • Published Date: 19 December 2018

      Abstract: The development of a vaccine based on human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the antibody production patterns of HIV-1 Env gp120 and hepatitis B virus surface antigen (HBsAg) to provide insights into how we may improve the protective efficacy of Env-based immunogens. Our previous study showed that HIV Env and HBsAg display different mechanisms of antibody elicitation and that T cells facilitate the responses to repeated immunizations. Here, to elucidate the detailed roles of primary immunization in immune memory response formation and antibody production, we immunized C57BL/6 mice with each antigen and evaluated the development of T follicular helper (Tfh) cells, germinal centers, and the memory responses involved in prime and boost immunizations. We found that after prime immunization, compared with HBsAg, gp120 induced higher frequencies of Tfh cells and programmed death (PD)-1+ T cells, greater major histocompatibility complex Ⅱ expression on B cells, comparable activated B cells, but weaker germinal center (GC) reactions and memory B cell responses in the draining lymph nodes, accompanied by slower antibody recall responses and poor immune memory responses. The above results suggested that more PD-1+ T cells arising in primary immunization may serve as major contributors to the slow antibody recall response elicited by HIV-1 Env.

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