HIV-1 infection induces B cell defects, not fully recovered upon antiretroviral therapy (ART). Acute infection and the early start of ART provide unique settings to address the impact of HIV on the B cell compartment. We took advantage of a cohort of 21 seroconverters, grouped according to the presence of severe manifestations likely mediated by antibodies or immune complexes, such as Guillain-Barré syndrome and autoimmune thrombocytopenic purpura, with a follow-up of 8 weeks upon effective ART. We combined B and T cell phenotyping with serum immunoglobulin level measurement and quantification of sj-KRECs and ΔB to estimate bone marrow output and peripheral proliferative history of B cells, respectively. We observed marked B cell disturbances, notably a significant expansion of cells expressing low levels of CD21, in parallel with markers of both impaired bone marrow output and increased peripheral B cell proliferation. This B cell dysregulation is likely to contribute to the severe immune-mediated conditions, as attested by the higher serum IgG and the reduced levels of sj-KRECs with increased ΔB in these individuals as compared to those patients with mild disease. Nevertheless, upon starting ART, the dynamic of B cell recovery was not distinct in the two groups, featuring both persistent alterations by week 8. Overall, we showed for the first time that acute HIV-1 infection is associated with decreased bone marrow B cell output assessed by sj-KRECs. Our study emphasizes the need to intervene in both bone marrow and peripheral responses to facilitate B cell recovery during acute HIV-1 infection.

HIV-1感染会诱导B细胞缺陷，但在抗逆转录病毒治疗（ART）后无法完全恢复。急性感染和ART的提早开始提供了独特的环境，以应对HIV对B细胞区室的影响。我们利用了21个血清转化者的队列，根据可能由抗体或免疫复合物介导的严重表现（如Guillain-Barré综合征和自身免疫性血小板减少性紫癜）进行分组，在有效抗逆转录病毒治疗后进行了8周的随访。我们将B和T细胞表型与血清免疫球蛋白水平测量相结合，并对sj-KRECs和ΔB进行定量，以分别估计骨髓输出和B细胞的外周增生史。我们观察到明显的B细胞干扰，尤其是表达低水平CD21的细胞显着扩增，与骨髓输出受损和外周B细胞增殖增加的标志物同时出现。与轻症患者相比，这些患者中较高的血清IgG和ΔB升高的sj-KRECs水平降低证明了这种B细胞调节异常可能导致了严重的免疫介导疾病。然而，在开始ART治疗后，两组的B细胞恢复动态并不明显，其特征是在第8周时都持续发生改变。总的来说，我们首次表明急性HIV-1感染与骨髓B细胞减少有关sj-KRECs评估的输出。我们的研究强调在急性HIV-1感染期间需要干预骨髓和外周反应以促进B细胞恢复。