Defining the Role of Marginal Zone B Cells in FVIII Inhibitor Development

The formation of factor VIII (FVIII) inhibitors in hemophilia A patients involves complex immune responses, including the activation of CD4 T cells and B cells. Marginal zone (MZ) B cells, an innate-like B cell population in the spleen, play a key role in the early stages of inhibitor development by rapidly responding to blood-borne antigens. These cells are uniquely positioned to capture and present FVIII to CD4 T cells, initiating a robust immune response that can lead to the formation of neutralizing antibodies. This chapter explores the critical role of MZ B cells in FVIII inhibitor development, focusing on their function in antigen presentation and their potential as therapeutic targets to prevent inhibitor formation. Using immunohistochemistry (IHC) and flow cytometry, we investigate the interactions between MZ B cells, CD4 T cells, and other immune components in the spleen, providing a deeper understanding of the molecular mechanisms underlying FVIII inhibitor development. By elucidating these immune interactions, we aim to inform the development of novel strategies to mitigate FVIII inhibitor formation in hemophilia A patients.