Department of Immunology and Serology, National AIDS Research Institute, Pune, Maharashtra, India.
AIDS. 2020 Sep 1;34(11):1603-1608. doi: 10.1097/QAD.0000000000002620.
The HIV-1-specific antibodies are being considered for prevention and therapy in HIV infection. For effective antibody response, presence of functionally competent memory B cells (MEBs) is important; however, HIV-infection is known to alter the B-cell functionality. Very limited data are available on the HIV-specific memory B-cell population in HIV-infected Indian population.
In this study, the frequencies of HIV-gp140-specific MEBs were measured in individuals with nonprogressive [long-term-nonprogressors (LTNPs), N = 20] and progressive (N = 19) HIV infection using multicolor flow cytometry. The activation and functional status of these MEBs were assessed as frequencies and mean fluorescence intensity (MFI) of the CD38 and CD40 expression, respectively.
The percentages of gp140 + MEBs were higher in LTNPs than seen in progressors (P = 0.0475) and associated with higher CD4 cell count (P = 0.0312, r = 0.2833). As compared with the progressors, LTNPs also showed higher functional (CD40+) gp140 + MEBs both frequencies (P < 0.0001) and CD40 MFI (P = 0.0222), whereas the frequencies (<0.0001) and the MFI (P = 0.0047) of CD38 expression was significantly lower. Higher CD4 cell counts and lower plasma viral load values were associated with higher frequencies of CD40+ gp140 + MEBs (P < 0.0001, r = 0.4962) (P = 0.0036, r = -0.4202) and lower frequencies (P = 0.0008, r = -0.4231) and CD38 expression (MFI) (P = 0.004, r = -0.3719) (P = 0.0066, r = 0.4033).
Our study suggests that LTNPs have functional HIV-specific memory B-cell compartment with reduced activation that may lead to effective HIV-specific humoral immune responses contributing to their nondisease progression status. These findings would help in better understanding of the characteristics of the HIV-specific memory B-cell population in nonprogressive HIV infection.
HIV-1 特异性抗体被认为可用于 HIV 感染的预防和治疗。为了产生有效的抗体反应，功能性记忆 B 细胞（MEB）的存在很重要；然而，HIV 感染已知会改变 B 细胞的功能。关于 HIV 感染的印度人群中 HIV 特异性记忆 B 细胞群体，仅有非常有限的数据。
本研究使用多色流式细胞术测量了无进展性[长期非进展者（LTNPs），N=20]和进展性 HIV 感染个体中 HIV-gp140 特异性 MEB 的频率。通过 CD38 和 CD40 表达的频率和平均荧光强度（MFI）分别评估这些 MEB 的激活和功能状态。
与进展者相比，LTNPs 中的 gp140+MEB 百分比更高（P=0.0475），并且与更高的 CD4 细胞计数相关（P=0.0312，r=0.2833）。与进展者相比，LTNPs 还显示出更高的功能性（CD40+）gp140+MEB 频率（P<0.0001）和 CD40 MFI（P=0.0222），而 CD38 表达的频率（<0.0001）和 MFI（P=0.0047）均较低。较高的 CD4 细胞计数和较低的血浆病毒载量值与 CD40+gp140+MEB 更高的频率相关（P<0.0001，r=0.4962）（P=0.0036，r=-0.4202）和更低的频率（P=0.0008，r=-0.4231）和 CD38 表达（MFI）（P=0.004，r=-0.3719）（P=0.0066，r=-0.4033）。
我们的研究表明，LTNPs 具有具有较低激活的功能性 HIV 特异性记忆 B 细胞区室，这可能导致有效的 HIV 特异性体液免疫反应，从而导致其非疾病进展状态。这些发现将有助于更好地了解非进展性 HIV 感染中 HIV 特异性记忆 B 细胞群体的特征。
