Nodal reactive proliferation of monocytoid B-cells may represent atypical memory B-cells

J Microbiol Immunol Infect. 2023 Aug;56(4):729-738. doi: 10.1016/j.jmii.2023.03.010. Epub 2023 Apr 11.

Abstract

Background: Reactive lymphadenopathies such as toxoplasmosis and cytomegalovirus lymphadenitis are associated with monocytoid cell proliferation. Monocytoid cells are B-lymphocytes with an undetermined subset.

Methods: Using digital spatial profiling whole transcriptome analyses, this study compared monocytoid and control B-cells. The B-cell subset of monocytoid cells was assigned according to gene expression profiles.

Results: This study identified 466 differentially expressed genes between monocytoid and control B-cells. The cellular deconvolution algorithm identified monocytoid cells as memory B-cells instead of as naïve B-cells. A comparison of the upregulated genes revealed that atypical memory B-cells had the largest number of genes overlapping with monocytoid cells compared with other memory B-cell subsets. Atypical memory B-cell markers, namely TBX21 (T-bet), FCRL4 (IRTA1), and ITGAX (CD11c), were all upregulated in monocytoid cells. Similar to atypical memory B-cells, monocytoid cells exhibited (1) upregulated transcription factors (TBX21, TOX), (2) upregulated genes associated with B-cell inhibition (FCRL5, FCRL4) and downregulated genes associated with B-cell activation (PIK3CG, NFKB1A, CD40), (3) downregulated cell cycle-related genes (CDK6, MYC), and (4) downregulated cytokine receptors (IL4R). This study also analyzed the expression of monocytoid cell signature genes in various memory B-cell subsets. Atypical memory B-cells exhibited a gene expression pattern similar to that of monocytoid cells, but other memory B-cell subsets did not. Furthermore, monocytoid cells and marginal zone lymphomas differed in gene expression profiles.

Conclusion: Spatial transcriptomic analyses indicated that monocytoid cells may be atypical memory B-cells.

Keywords: Age-associated B-cells; Gene expression; GeoMx; Memory B-cells; Monocytoid cells.

MeSH terms

  • B-Lymphocyte Subsets* / metabolism
  • B-Lymphocyte Subsets* / pathology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Cell Proliferation
  • Humans
  • Lymph Nodes / pathology
  • Lymphoma, B-Cell, Marginal Zone* / genetics
  • Lymphoma, B-Cell, Marginal Zone* / metabolism
  • Lymphoma, B-Cell, Marginal Zone* / pathology