Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells

Biology Biology
Genomics Genomics
Immunology Immunology
Infectious Disease Infectious Disease
Alex K. Shalek Alex K. Shalek
Ira Fleming Ira Fleming

Jiang et al.▾ Jiang, R., Meng, H., Raddassi, K., Fleming, I., Hoehn, K.B., Dardick, K.R., Belperron, A.A., Montgomery, R.R., Shalek, A.K., Hafler, D.A., Kleinstein, S.H.#, Bockenstedt, L.K.#

JCI Insight , Volume 6

June, 2021


The skin lesion erythema migrans (EM) is an initial sign of the Ixodes tick–transmitted Borreliella spirochetal infection known as Lyme disease. T cells and innate immune cells have previously been shown to predominate the EM lesion and promote the reaction. Despite the established importance of B cells and antibodies in preventing infection, the role of B cells in the skin immune response to Borreliella is unknown. Here, we used single-cell RNA-Seq in conjunction with B cell receptor (BCR) sequencing to immunophenotype EM lesions and their associated B cells and BCR repertoires. We found that B cells were more abundant in EM in comparison with autologous uninvolved skin; many were clonally expanded and had circulating relatives. EM-associated B cells upregulated the expression of MHC class II genes and exhibited preferential IgM isotype usage. A subset also exhibited low levels of somatic hypermutation despite a gene expression profile consistent with memory B cells. Our study demonstrates that single-cell gene expression with paired BCR sequencing can be used to interrogate the sparse B cell populations in human skin and reveals that B cells in the skin infection site in early Lyme disease expressed a phenotype consistent with local antigen presentation and antibody production.