Ectopic Lymphoid Follicles in Multiple Sclerosis: Centers for Disease Control?

Area of Science:

• Immunology
• Neuroimmunology
• Pathogenesis of Multiple Sclerosis

Background:

• Autoreactive CD4+ T cells are implicated in Multiple Sclerosis (MS).
• B cell-depleting therapies highlight the complex role of B cells in MS pathogenesis.
• B cells contribute via antibody-dependent and -independent mechanisms.

Purpose of the Study:

• To review evidence on B cells as drivers of MS.
• To examine the role of germinal center (GC)-like ectopic lymphoid follicles (eLFs) in MS pathogenesis.
• To explore mechanisms regulating GC-derived autoreactive B cell responses in MS.

Main Methods:

• Review of human and animal model studies.
• Analysis of B cell and T cell responses within germinal centers.
• Investigation of ectopic lymphoid follicles (eLFs) in MS.

Main Results:

• Germinal centers (GCs) are critical for B cell activation and differentiation, requiring T follicular helper (Tfh) cells.
• B cells, including antibody-secreting cells (ASCs) and memory B cells, play significant roles.
• MS patients exhibit GC-like eLFs in the meninges, with elevated CXCL13 and Tfh cells, but lacking regulatory Tfr cells.

Conclusions:

• GCs are central to generating and regulating autoreactive B and T cell responses in MS.
• eLFs in MS patients may represent sites of pathogenic immune responses.
• Targeting GCs and eLFs offers potential therapeutic strategies for MS.