Background/Purpose: Complement and B cells are implicated in the pathophysiology of rheumatoid arthritis, an autoimmune disease characterized by synovial inflammation. Loss of complement regulator CD55 leads to delayed onset of inflammatory arthritis in the collagen-induced mouse model of arthritis (CIA).¹ Marginal zone (MZ) B cells, an innate-like B cell population, serve as first responders to blood-borne pathogens by rapidly differentiating into antibody producing plasmablasts, and are important initiators of CIA.² Whether and how CD55 regulates MZ B cells in CIA pathogenesis is unknown.

Methods: We examined naïve and sorted MZ B cell populations in 3-5 week-old and 10-12 week-old CD55-/- and compared to wildtype (WT) C57BL/6 mice using flow cytometry, immunofluorescence, bromodeoxyuridine (BrdU) incorporation, and bulk RNAseq. Differential gene expression analysis was performed, followed by Gene Sequence Enrichment Analysis (GSEA).

Results: We found that loss of CD55 decreased the number of MZ B cells in 10-12 week-old, but not 3-5 week-old mice. The precursors to MZ B cells were unchanged at both endpoints, indicating that loss of MZ B cells was not due to failure of MZ B cell differentiation. En vivo BrdU incorporation showed no difference between CD55-/- and WT, indicating MZ B cell differences are not due to loss of proliferative capacity. Differential gene expression analysis showed decreased expression of genes involved in preventing apoptosis in MZ B cells of CD55-/- compared to WT mice (HSP90b1, STIP1, AHSA1, and FKBP4). GSEA showed decreased expression of cell cycle/cell survival pathways in CD55-/- cells relative to WT. Flow cytometry revealed that CD55-/- MZ B cells had corresponding increases in activated caspase-3 and caspase-7.

Conclusion: Loss of CD55 led to increased reactive oxygen species and activation of caspases in MZ B cell populations, which may prevent the normal expansion of the MZ B cell subset over time. These studies suggest a role for the complement regulator CD55 in MZ B cell homeostasis and survival. Future experiments are aimed at defining whether loss of CD55 impacts MZ B cell survival through complement dependent or independent mechanisms.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/loss-of-the-complement-regulator-cd55-alters-marginal-zone-b-cell-homeostasis/