Adoptive Transfer of Memory B Cells

Zuccarino-Catania, Griselda; Shlomchik, Mark J.

doi:10.21769/bioprotoc.1563

Cited by 8 publications

(3 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(1x10 7 cells/mouse) into NSG mice 4 weeks post PFFs injection. The optimal number of T and B cells for adoptive transfer ranges from 1x10 6 -1x10 7 cells/mouse [41][42][43][44][45][46]. Purification of T and B cells from total splenocytes was carried out by negative selection using Dynabeads untouched mouse T cells and Dynabeads untouched CD43 B cells isolation kits according to the manufacturer's instruction (Invitrogen).…”

Section: Adoptive Transfermentioning

confidence: 99%

T cells limit accumulation of aggregate pathology following intrastriatal injection of α-synuclein fibrils

George¹,

Tyson²,

Rey

et al. 2020

Preprint

View full text Add to dashboard Cite

α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of αsynucleinopathies, such as Parkinson's disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells.These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease.To study the role of the adaptive immune system with respect to α-syn pathology, we injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology as well as microgliosis. Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. We also reconstituted T and B cell populations in the NSG mice with cells isolated from a wildtype mouse spleen. Interestingly, reconstituting the T cell population decreased the accumulation of α-syn pathology and resulted in persistent microgliosis when compared to non-transplanted mice; reconstitution of B cells did not alter the nigral neuropathology. Our work provides experimental evidence that T cells play a role in the pathogenesis of α-synucleinopathies.

show abstract

Section: Adoptive Transfermentioning

confidence: 99%

T cells limit accumulation of aggregate pathology following intrastriatal injection of α-synuclein fibrils

George¹,

Tyson²,

Rey

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…To study antigen-specific ABCs after immunization, we transferred PfCSP-specific Igh g2A10 cells ( 37 ) to MD4 recipients and immunized with Plasmodium berghei –PfCSP sporozoites (PfCSP-SPZ) that express the PfCSP in place of the endogenous P. berghei CSP protein (PbCSP) ( 38 ). The use of the MD4 recipient Ig-transgenic mice that express an irrelevant BCR (hen egg lysozyme) is an established approach for the study of rare memory cell populations ( 39 ). Additionally, we confirmed that the Igh g2A10 B cell did not respond to noncognate antigen or SPZs under such settings (fig.…”

Section: Resultsmentioning

confidence: 99%

Zeb2 drives the formation of CD11c ⁺ atypical B cells to sustain germinal centers that control persistent infection

Gao,

Shen,

Roco

et al. 2024

Sci. Immunol.

View full text Add to dashboard Cite

CD11c + atypical B cells (ABCs) are an alternative memory B cell lineage associated with immunization, infection, and autoimmunity. However, the factors that drive the transcriptional program of ABCs have not been identified, and the function of this population remains incompletely understood. Here we identified candidate transcription factors associated with the ABC population based on a human tonsillar B cell single cell dataset. We identified CD11c + B cells in mice with a similar transcriptomic signature to human ABCs, and using an optimized CRISPR-Cas9 knockdown screen, we observed that loss of zinc finger E-box binding homeobox 2 (Zeb2) impaired ABC formation. Furthermore, ZEB2 haplo-insufficient Mowat Wilson syndrome (MWS) patients have decreased circulating ABCs in the blood. In Cd23 Cre/+ Zeb2 fl/fl mice with impaired ABC formation, ABCs were dispensable for efficient humoral responses after Plasmodium sporozoite immunization but were required to control recrudescent blood-stage malaria. Immune phenotyping revealed that ABCs drive optimal T follicular helper (Tfh) cell formation and germinal center (GC) responses and they reside at the red/white pulp border likely permitting better access to pathogen antigens for presentation. Collectively, our study shows that ABC formation is dependent upon Zeb2, and these cells can limit recrudescent infection by sustaining GC reactions.

show abstract

“…To assess this we transferred PfCSP-specific Igh g2A10 cells (28) to MD4 recipients and immunized with P. berghei -PfCSP sporozoites (PfCSP-SPZ) that express PfCSP in place of the endogenous P. berghei CSP protein (29). The use of recipient Ig-transgenic mice which express an irrelevant BCR - in this case specific for hen egg lysozyme - is an established approach for the study of rare memory cell populations (30). Immune responses were assessed 4, 10 and 21 days post-immunization ( Figure 2A ).…”

Section: Resultsmentioning

confidence: 99%

ZEB2 regulates the development of CD11c+ atypical B cells

Gao

Shen

Roco

et al. 2022

Preprint

View full text Add to dashboard Cite

CD11c+ atypical B cells (ABC) are an alternative memory B cell lineage identified both in normal immune responses as well as pathogenic responses in autoimmunity. While it is clear that ABCs have a distinct transcriptional program, the factors that direct this program have not been identified. Here, we generated a human tonsil single-cell RNA-seq dataset and identified candidate transcription factors associated with the ABC population. We selected 8 of these transcription factors for further analysis based on their conserved expression in mouse ABC bulk RNA-seq datasets. Using an optimized CRSPR-Cas9 knockdown method we found that only zinc finger E-box binding homeobox 2 (Zeb2) knock-out impaired ABC formation. To assess the role of Zeb2 in ABC formation in vivo we used Zeb2fl/fl mice crossed to a CD23Cre line. Germinal center and plasma cell responses in these mice after Plasmodium sporozoite immunization were largely unaltered but we observed a specific defect in ABC formation. We further determined that ZEB2 haploinsufficient Mowat Wilson syndrome patients also have decreased circulating ABCs in the blood, supporting a role for this transcription factor in humans as well as mice. In sum, we identified Zeb2 as a key TF governing the formation of ABCs.

show abstract

Adoptive Transfer of Memory B Cells

Cited by 8 publications

References 8 publications

T cells limit accumulation of aggregate pathology following intrastriatal injection of α-synuclein fibrils

T cells limit accumulation of aggregate pathology following intrastriatal injection of α-synuclein fibrils

Zeb2 drives the formation of CD11c ⁺ atypical B cells to sustain germinal centers that control persistent infection

ZEB2 regulates the development of CD11c+ atypical B cells

Contact Info

Product

Resources

About

Adoptive Transfer of Memory B Cells

Cited by 8 publications

References 8 publications

T cells limit accumulation of aggregate pathology following intrastriatal injection of α-synuclein fibrils

T cells limit accumulation of aggregate pathology following intrastriatal injection of α-synuclein fibrils

Zeb2 drives the formation of CD11c + atypical B cells to sustain germinal centers that control persistent infection

ZEB2 regulates the development of CD11c+ atypical B cells

Contact Info

Product

Resources

About

Zeb2 drives the formation of CD11c ⁺ atypical B cells to sustain germinal centers that control persistent infection