Shared transcriptional profiles of atypical B cells suggest common drivers of expansion and function in malaria, HIV, and autoimmunity.
Prasida HollaBrian L P DizonAbhijit A AmbegaonkarNoga RogelElla GoldschmidtArun K BoddapatiHaewon SohnDan SturdevantJames W AustinLela KardavaYue-Sheng LiPoching LiuSusan L MoirSusan K PierceAsaf MadiPublished in: Science advances (2021)
Chronic infectious diseases have a substantial impact on the human B cell compartment including a notable expansion of B cells here termed atypical B cells (ABCs). Using unbiased single-cell RNA sequencing (scRNA-seq), we uncovered and characterized heterogeneities in naïve B cell, classical memory B cells, and ABC subsets. We showed remarkably similar transcriptional profiles for ABC clusters in malaria, HIV, and autoimmune diseases and demonstrated that interferon-γ drove the expansion of ABCs in malaria. These observations suggest that ABCs represent a separate B cell lineage with a common inducer that further diversifies and acquires disease-specific characteristics and functions. In malaria, we identified ABC subsets based on isotype expression that differed in expansion in African children and in B cell receptor repertoire characteristics. Of particular interest, IgD+IgMlo and IgD-IgG+ ABCs acquired a high antigen affinity threshold for activation, suggesting that ABCs may limit autoimmune responses to low-affinity self-antigens in chronic malaria.
Keyphrases
- single cell
- plasmodium falciparum
- rna seq
- antiretroviral therapy
- infectious diseases
- hiv infected
- human immunodeficiency virus
- gene expression
- hiv testing
- hepatitis c virus
- young adults
- hiv aids
- poor prognosis
- endothelial cells
- transcription factor
- dendritic cells
- multiple sclerosis
- men who have sex with men
- peripheral blood
- genome wide
- immune response
- drug induced
- mass spectrometry
- capillary electrophoresis