Rosenberg Y J, Lewis M G, Greenhouse J J, Cafaro A, Leon E C, Brown C R, Bieg K E, Kosco-Vilbois M H
Therimmune Inc., Rockville, MD, USA.
Eur J Immunol. 1997 Dec;27(12):3214-22. doi: 10.1002/eji.1830271219.
HIV and simian immunodeficiency virus (SIV) infections are characterized by several abnormalities in B cell function. Pathogenesis is also associated with marked changes within germinal centers (GC) including hypertrophy and degeneration of follicular dendritic cells (FDC) and accumulation of both viral antigen and activated CD45RO+ CD8+ cells. Since FDC are critical to the generation of antibody-forming cells and specific B cell memory, the simplest assumption is that such B cell defects directly result from virus-induced changes in the GC environment. The present study examined FDC-enriched mesenteric lymph node lymphocyte preparations from early and late stage SIV-infected and uninfected macaques for their ability to support GC reactions in vitro. The results indicate that FDC function as measured by cluster formation, B cell proliferation and SIV-specific antibody production is enhanced in SIV-infected macaques suggesting that, despite FDC atrophy, virus accumulation induces increased FDC-B cell interactions resulting in B cell hyperactivity. The activation and proliferation of CD8+ cells in FDC-enriched cultures further suggest that the infiltrating CD8+ population observed in situ in GC of late-stage SIV/HIV-infected individuals may also benefit from FDC-derived growth signals. Thus, in addition to enhanced B cell proliferation and antibody production, hyperactivity of FDC may potentially promote their own self destruction via the infiltrating CD8+ cells. The increased B cell responsiveness may further exacerbate the disease process due to an overall decrease in the affinity of anti-HIV/SIV antibody, a loss of crucial protective antibodies to other infectious agents and the creation of an environment in which increased trapping of virions facilitates more extensive infection of CD4+ T cells.
HIV和猴免疫缺陷病毒（SIV）感染的特征是B细胞功能存在多种异常。发病机制还与生发中心（GC）内的显著变化有关，包括滤泡树突状细胞（FDC）的肥大和退化，以及病毒抗原和活化的CD45RO + CD8 +细胞的积累。由于FDC对于抗体形成细胞的产生和特异性B细胞记忆至关重要，最简单的假设是这种B细胞缺陷直接源于病毒诱导的GC环境变化。本研究检测了来自早期和晚期SIV感染及未感染猕猴的富含FDC的肠系膜淋巴结淋巴细胞制剂在体外支持GC反应的能力。结果表明，通过簇形成、B细胞增殖和SIV特异性抗体产生来衡量的FDC功能在SIV感染的猕猴中增强，这表明尽管FDC萎缩，但病毒积累会诱导FDC与B细胞之间的相互作用增加，从而导致B细胞活性增强。富含FDC的培养物中CD8 +细胞的活化和增殖进一步表明，在晚期SIV / HIV感染个体的GC中原位观察到的浸润性CD8 +群体也可能受益于FDC衍生的生长信号。因此，除了增强B细胞增殖和抗体产生外，FDC的活性增强可能会通过浸润的CD8 +细胞潜在地促进其自身的自我破坏。B细胞反应性增加可能会由于抗HIV / SIV抗体亲和力的总体下降、对其他传染原的关键保护性抗体的丧失以及创造了一种病毒颗粒捕获增加促进CD4 + T细胞更广泛感染的环境而进一步加剧疾病进程。
