. 2020 Jul 29;18(2):294–306. doi: 10.1038/s41423-020-0510-z

Table 2.

Relevance of B cell subsets in autoimmune neurological diseases and future directions

B cell subset^a	Phenotype	Relevance in disease	Future directions
Transitional/ new emigrant B cells	CD19+CD20+CD21^loCD10+IgM^hi	Periphery MG and NMOSD: Increased autoreactivity and polyreactivity due to impaired central tolerance^49,50	MG and NMOSD: - Investigate whether polyreactive and autoreactive naïve B cells differentiate into disease-specific memory and antibody-secreting cells, which contribute to disease.
Naïve B cells	CD19+CD20+CD27−IgD+	Periphery NMOSD: Secretion of AQP4-IgG when cultured with ASCs in vitro²¹ MG and NMOSD: Increased autoreactivity and polyreactivity due to impaired peripheral tolerance^49,50
Memory B cells	Traditional: CD19+CD20+CD27+IgD−	Periphery NMOSD: Secretion of AQP4-IgG in culture,²¹ relation to CSF plasmablasts,⁵⁷ reduction in relapse when treated upon re-emergence after rituximab²⁸ MuSK MG: MuSK specificity identified²⁰ CSF NMOSD: Clonally related to peripheral B cells⁵⁷ NMDAR: NR1 specificity identified⁴⁸	MuSK MG: - Elucidate potential selection bias of MuSK tetramers on the isolation MuSK-specific B cells. NMDAR: - Investigate the presence of additional pathogenic epitopes, as many memory B cell- and ASC-derived rAbs bound strongly to epitopes outside of NR1. - Determine the relationship between antibody titer and affinity with clinical disease progression.
Memory B cells	Double-negative: CD19+CD20+CD27+IgD−	Periphery NMOSD: Closest relation to CSF plasmablasts⁵⁷
Plasmablasts	CD19+CD20+CD27+CD38+	Periphery MuSK MG: Rituximab-induced depletion of MuSK antibody titers,⁴³ MuSK specificity identified^20,45 NMDAR: Rituximab-induced incomplete depletion of plasmablasts⁴⁶ CSF NMOSD: AQP4 specificity identified,⁷⁵ decreased risk of relapse on satralizumab³⁹, may have peripheral⁵⁷ or CNS origins⁷⁵ NMDAR: NR1 specificity identified⁴⁸	MuSK MG: - Study the relevance of IgG subgroups and epitopes in clinical disease manifestations. NMDAR: - Compare recombinant antibodies cloned from various neurological disorders with anti-NMDAR antibodies to find distinct features to characterize each disease phenotype.
Plasma cells	CD27+CD38+CD138+	Periphery AChR MG: AChR antibody secretion unaffected by rituximab,⁴³ spontaneous production of AChR antibodies⁴⁴ CSF NMOSD: AQP4 specificity and pathogenicity identified²⁵ NMDAR: NR1 specificity and pathogenicity identified⁸⁶	NMDAR: - Investigate the compartment in which affinity maturation of autoreactive B cells occurs.

^aStill largely unexplored in MOGAD