Preprint: Specific induction of double negative B cells during protective and pathogenic immune responses, 2020, Ruschil et al

[Andy]

Double negative (DN) (CD19+CD20lowCD27-IgD-) B cells are expanded in patients with autoimmune and infectious diseases; however their role in the humoral immune response remains unclear. Using systematic flow cytometric analyses of peripheral blood B cell subsets, we observed an inflated DN B cell population in patients with variety of active inflammatory conditions: myasthenia gravis, Guillain-Barre syndrome, neuromyelitis optica spectrum disorder, meningitis/encephalitis, and rheumatic disorders. Furthermore, we were able to induce DN B cells in healthy subjects following vaccination against influenza and tick borne encephalitis virus. Transcriptome analysis revealed a gene expression profile in DN B cells that clustered with naive B cells, memory B cells, and plasmablasts. Immunoglobulin VH transcriptome sequencing and analysis of recombinant antibodies revealed clonal expansion of DN B cells, that were targeted against the vaccine antigen. Our study suggests that DN B cells are expanded in multiple inflammatory neurologic diseases and represent an inducible B cell population that responds to antigenic stimulation, possibly through an extra-follicular maturation pathway

https://www.biorxiv.org/content/10.1101/2020.09.08.285148v1?ct=

 

[Snow Leopard]

However, DN B cells appear to be a heterogenic B cell subset (30) and have been suggested to represent either exhausted memory B cells / senescent B cells (31), transient effector B cells or a unique atypical memory-like B cells, which may be relevant for plasmablast generation (32,33). More recently, detailed studies in SLE indicated that a subset of DN B cells might be derived from an activated naïve B cell subset and further differentiate into plasmablasts through an extra-follicular maturation pathway (1).

Low CD20 means Rituximab will have limited clinical response if these cells are pathogenic.

Notably, they did not find an association of increased DN B cells with age, unlike other studies.