Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

Robinson, Marc; Ding, Zhoujie; Dowling, Mark R.; Hill, Danika L.; Webster, Rosela H.; McKenzie, Craig; Pitt, Catherine; O’Donnell, Kristy; Mulder, Jesse; Brodie, Erica J.; Hodgkin, Philip D.; Wong, Nicholas C.; Quast, Isaak; Tarlinton, David M.

doi:10.1016/j.immuni.2023.04.015

Cited by 39 publications

(14 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Congruent with our first observations in mouse and human, these results also suggest that cluster C is less likely to be found in lymphoid tissues. Our findings are in line with recent works suggesting that PC longevity determination results from the integration of extrinsic and intrinsic cues and reporting markers for long-lived PC subsets 1,11,18,19 . How these subsets may overlap with the one described here will require further investigation.…”

Section: Resultssupporting

confidence: 93%

Plasma cell heterogeneity is driven by type of immune challenge

Khamyath,

Lereclus,

Gourhand

et al. 2024

Preprint

View full text Add to dashboard Cite

Plasma cells play an essential role in humoral immunity, but many questions remain regarding the heterogeneity of this population, both in terms of ontogeny and involvement in the immune response. In this work, we have identified 5 subsets of plasma cells in human and mouse lymphoid tissues. These subpopulations were distinguished by differential expression of CD62L, CXCR4, FcgRIIb and CD93. The antigenic context as well as the B cell of origin directed plasma cell differentiation towards specific subtypes that display distinct migratory and survival abilities in vivo. Altogether, our results unveil that plasma cell phenotypic and functional heterogeneity relies on intrinsic imprinting during B cell activation.

show abstract

Section: Resultssupporting

confidence: 93%

Plasma cell heterogeneity is driven by type of immune challenge

Khamyath,

Lereclus,

Gourhand

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…ASCs include 2 major populations: 1) proliferative, relatively immature and short-lived PBs and 2) post-mitotic, mature PCs with long-lived potential. In mice, CD45R(B220) expression can be used to delineate between these 2 populations ( Figure 3A ) 9,10,25,26 . In all 3 organs examined, DTR levels were increased in PBs and PCs from J-DTR mice compared to cells from WT animals ( Figures 3F-3H ).…”

Section: Resultsmentioning

confidence: 99%

“…Multiple groups have developed genetic models to fluorescently timestamp ASCs which have led to new insights regarding ASC longevity as well as the developmental relationship between short-lived plasmablasts (PBs) and post-mitotic plasma cells (PCs) 7,[9][10][11] . Many of these experiments have been performed in the context of a fully replete ASC compartment constraining the ability to assess ASC longevity in competitive versus noncompetitive scenarios.…”

Section: Introductionmentioning

confidence: 99%

Jchain-DTRMice Allow for Diphtheria Toxin-Mediated Depletion of Antibody-Secreting Cells and Evaluation of Their Differentiation Kinetics

Pioli,

Ritchie,

Haq

et al. 2024

Preprint

View full text Add to dashboard Cite

Antibody-secreting cells (ASCs) are generated following B cell activation and constitutively secrete antibodies. As such, ASCs are key mediators of humoral immunity whether it be in the context of pathogen exposure, vaccination or even homeostatic clearance of cellular debris. Therefore, understanding basic tenants of ASC biology such as their differentiation kinetics following B cell stimulation is of importance. Towards that aim, we developed a mouse model which expresses simian HBEGF (a.k.a., diphtheria toxin receptor (DTR)) under the control of the endogenous Jchain locus (or J-DTR). ASCs from these mice expressed high levels of cell surface DTR and were acutely depleted following diphtheria toxin treatment. Furthermore, proof-of-principle experiments demonstrated the ability to use these mice to track ASC reconstitution following depletion in 3 distinct organs. Overall, J-DTR mice provide a new and highly effective genetic tool allowing for the study of ASC biology in a wide range of potential applications.

show abstract

“…Acute live viral infection in mice can lead to long-lasting antiviral serum Abs in both B6 and BALB/c mice 40 . At present, the mechanistic linkage between immediate and long-term Ab production upon viral infection or vaccination has not been fully established 41, 42 . This is due in part to the inherent complexity of studies of viral infections, as well as the empirical use of adjuvants or the complex ingredients of commonly studied VLPs.…”

Section: Discussionmentioning

confidence: 99%

“…Our current study has exclusively focused on the primary Ab responses to SVLS at a very low Ag dose. At present, the relationship between short-term expansion of plasmablasts and generation of long-lived plasma cells for durable protection is being actively studied (27,107). It is thus notable that all the IgG responses to SVLS are long-lived (Fig.…”

Section: (4) Role Of Cd19 In B Cell Response Towards Virus-like Agsmentioning

confidence: 99%

Minimal determinants for lifelong antiviral antibody responses in BALB/c mice from a single exposure to virus-like immunogens at low doses

Wholey

Meyer

Yoda

et al. 2023

Preprint

View full text Add to dashboard Cite

Class-switched neutralizing antibody production is rapidly induced upon many viral infections and often long-lived, but the underlying mechanisms remain incompletely understood. Here we show that several features of this antibody response can be reconstituted by synthetic virus-like structures containing minimal, highly purified biochemical ingredients commonly found in enveloped viruses, and without viral replication or any other adjuvants. These findings reveal a shared mechanism for the production of neutralizing antibodies upon viral infection. High epitope density is capable but not necessary for driving antibody secretion. Instead, even a few molecules of surface antigen, when combined with nucleic acids within these structures, can trigger strong antiviral IgG production. As a result, B cells integrate both signals from individual viral particulate antigens to initiate a neutralizing IgG response.

show abstract

Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan

Cited by 39 publications

References 68 publications

Plasma cell heterogeneity is driven by type of immune challenge

Plasma cell heterogeneity is driven by type of immune challenge

Jchain-DTRMice Allow for Diphtheria Toxin-Mediated Depletion of Antibody-Secreting Cells and Evaluation of Their Differentiation Kinetics

Minimal determinants for lifelong antiviral antibody responses in BALB/c mice from a single exposure to virus-like immunogens at low doses

Contact Info

Product

Resources

About