Does the central nervous system (CNS) have germinal centers?

Germinal Centers in the Central Nervous System

The central nervous system (CNS) does not normally contain germinal centers, but they can form in pathological conditions such as chronic inflammation and certain autoimmune diseases.

Normal CNS Immune Environment

• The CNS has traditionally been considered an "immune privileged" site with tightly regulated immune responses 1
• Under normal physiological conditions:
  • Immune cell migration into the CNS is kept at very low levels 1
  • The blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier strictly control immune cell entry 1
  • The unique CNS microenvironment tightly regulates immune reactions 2

Pathological Formation of Germinal Centers in CNS

Germinal centers can form in the CNS under specific pathological conditions:

Multiple Sclerosis (MS)

• Ectopic lymphoid follicle-like structures containing germinal centers have been detected in the cerebral meninges of patients with secondary progressive MS 3
• These structures contain:
  • B cells, T cells, and plasma cells
  • Networks of follicular dendritic cells producing CXCL13
  • Proliferating B cells suggestive of germinal center formation 3
• Notably, these structures were found in secondary progressive MS but not in relapsing-remitting or primary progressive MS 3

Experimental Autoimmune Encephalomyelitis (EAE)

• In MP4-induced EAE (a B cell-dependent mouse model of MS):
  • B cell aggregates with CXCL13+ and germinal center CD10+ B cells form in the CNS
  • These structures show evidence of autonomous B cell-mediated autoimmunity 4
  • Germline transcripts are expressed in the CNS, particularly related to TH17-associated isotypes 4

CNS Lymphomas

• Primary CNS lymphomas (PCNSL) are aggressive neoplasms limited to the CNS 5
• Most PCNSLs are diffuse large B-cell lymphomas (DLBCL) 5
• However, these are not normal germinal centers but pathological proliferations of B cells

Clinical Significance

• The formation of ectopic lymphoid follicles with germinal centers in the CNS represents a critical step in maintaining humoral autoimmunity in diseases like MS 3
• These structures may play a role in:
  • Sustaining immunopathological processes
  • Disease exacerbation
  • CNS-restricted spreading of antigen-specific B cell responses 4
  • Maintenance and expansion of local autoimmune responses 2

Important Distinctions

• Germinal centers are not found in normal CNS tissue
• When present, they are located primarily in the meninges, not in the CNS parenchyma 3
• Their presence indicates chronic inflammation and ongoing B cell-related immune activity 4
• The biology of DLBCL in the CNS is distinct from germinal center B-cell origin in peripheral lymphomas 5

In conclusion, while the normal CNS lacks germinal centers, these structures can develop under pathological conditions, particularly in chronic inflammatory and autoimmune diseases affecting the CNS.