Patterns of ANA+ B cells for SLE patient stratification

Suurmond, Jolien; Atisha‐Fregoso, Yemil; Barlev, Ashley N.; Calderon, Silvia A.; Mackay, Meggan; Aranow, Cynthia; Diamond, Betty

doi:10.1172/jci.insight.127885

Cited by 30 publications

(30 citation statements)

References 43 publications

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“…Staining of NP-specific B cells from immunized mice was performed as previously described (59). Briefly, NP 6 -BSA-biotin was preincubated with streptavidin-APC (Thermo Fisher Scientific) on ice for 30 minutes, after which cells were incubated with NP 6 -BSA-biotin + streptavidin-APC on ice for 30 minutes.…”

Section: Methodsmentioning

confidence: 99%

Follicular dendritic cell dysfunction contributes to impaired antigen-specific humoral responses in sepsis-surviving mice

Rana¹,

Bella²,

Lederman³

et al. 2021

Journal of Clinical Investigation

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Section: Methodsmentioning

confidence: 99%

Follicular dendritic cell dysfunction contributes to impaired antigen-specific humoral responses in sepsis-surviving mice

Rana¹,

Bella²,

Lederman³

et al. 2021

Journal of Clinical Investigation

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“…By limiting the sequestration of free BAFF, decreased TACI expression may thereby allow reduced concentrations of locally generated BAFF to modulate GC selection via interaction with BAFF-R. 97 Importantly, recent studies suggest that, as in mice, the drive toward either the GC or EF pathway in SLE may be patient dependent, resulting in differences in the accumulation of autoreactive class switched memory cells vs plasma cells in individual lupus patients. 98 Cumulatively, these murine and human data indicate that significant complexity underlies lupus pathogenesis with both EF and GC-dependent B cell activation pathways contributing to pathogenic autoantibody production in SLE. More importantly, this complexity may explain contradictory data from human clinical trials.…”

Section: Distinct Contribution Of Ef and Gc Pathways To Lupus Pathomentioning

confidence: 98%

“…98 In contrast, TACI deletion exerted no impact on serum autoantibodies, plasma cell numbers and lifespan in NZM2328 lupus-prone mice, a model characterized by spontaneous GC formation and long-lived plasma cell expansion. Notably, in each of these strains, autoantibody secreting plasma cells are believed to be generated predominantly by an EF activation pathway.…”

Section: Taci Deletion Limited Disease Progression In Both the Mrl Famentioning

confidence: 99%

“…Notably, in each of these strains, autoantibody secreting plasma cells are believed to be generated predominantly by an EF activation pathway. 98 In contrast, TACI deletion exerted no impact on serum autoantibodies, plasma cell numbers and lifespan in NZM2328 lupus-prone mice, a model characterized by spontaneous GC formation and long-lived plasma cell expansion. 100 Importantly, these data are consistent with the known requirement for TACI signals in T cell-independent, but not T-celldependent, antibody responses.…”

Section: Tacimentioning

confidence: 99%

“…These findings suggest that increased serum BAFF and therapeutic BAFF inhibition could reciprocally modulate GC selection via either enhancing selection or deletion of autoreactive clones.Importantly, recent studies suggest that, as in mice, the drive toward either the GC or EF pathway in SLE may be patient dependent, resulting in differences in the accumulation of autoreactive class switched memory cells vs plasma cells in individual lupus patients 98. By limiting the sequestration of free BAFF, decreased TACI expression may thereby allow reduced concentrations of locally generated BAFF to modulate GC selection via interaction with BAFF-R. 97 These data are compatible with the general model wherein higher affinity B cells present more antigen to Tfh cells and thereby receive enhanced survival signals, including BAFF.…”

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confidence: 99%

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BAFF inhibition in SLE—Is tolerance restored?

Jackson

Davidson

2019

Immunological Reviews

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The B cell activating factor (BAFF) inhibitor, belimumab, is the first biologic drug approved for the treatment of SLE, and exhibits modest, but durable, efficacy in decreasing disease flares and organ damage. BAFF and its homolog APRIL are TNF‐like cytokines that support the survival and differentiation of B cells at distinct developmental stages. BAFF is a crucial survival factor for transitional and mature B cells that acts as rheostat for the maturation of low‐affinity autoreactive cells. In addition, BAFF augments innate B cell responses via complex interactions with the B cell receptor (BCR) and Toll like receptor (TLR) pathways. In this manner, BAFF impacts autoreactive B cell activation via extrafollicular pathways and fine tunes affinity selection within germinal centers (GC). Finally, BAFF and APRIL support plasma cell survival, with differential impacts on IgM‐ and IgG‐producing populations. Therapeutically, BAFF and combined BAFF/APRIL inhibition delays disease onset in diverse murine lupus strains, although responsiveness to BAFF inhibition is model dependent, in keeping with heterogeneity in clinical responses to belimumab treatment in humans. In this review, we discuss the mechanisms whereby BAFF/APRIL signals promote autoreactive B cell activation, discuss whether altered selection accounts for therapeutic benefits of BAFF inhibition, and address whether new insights into BAFF/APRIL family complexity can be exploited to improve human lupus treatments.

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Group 3 Innate Lymphoid Cells Exacerbate Lupus Nephritis by Promoting B Cell Activation in Kidney Ectopic Lymphoid Structures

Li,

Liang,

Zhong

et al. 2023

Advanced Science

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Group 3 innate lymphoid cells (ILC3s) represent a new population in immune regulation, yet their role in lupus nephritis (LN) remains elusive. In the present work, systemic increases in ILC3s, particularly in the kidney, are observed to correlate strongly with disease severity in both human and murine LN. Using MRL/lpr lupus mice and a nephrotoxic serum‐induced LN model, this study demonstrates that ILC3s accumulated in the kidney migrate predominantly from the intestine. Furthermore, intestinal ILC3s accelerate LN progression, manifested by exacerbated autoimmunity and kidney injuries. In LN kidneys, ILC3s are located adjacent to B cells within ectopic lymphoid structures (ELS), directly activating B cell differentiation into plasma cells and antibody production in a Delta‐like1 (DLL1)/Notch‐dependent manner. Blocking DLL1 attenuates ILC3s’ effects and protects against LN. Altogether, these findings reveal a novel pathogenic role of ILC3s in B cell activation, renal ELS formation and autoimmune injuries during LN, shedding light on the therapeutic value of targeting ILC3s for LN.

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Patterns of ANA+ B cells for SLE patient stratification

Cited by 30 publications

References 43 publications

Follicular dendritic cell dysfunction contributes to impaired antigen-specific humoral responses in sepsis-surviving mice

Follicular dendritic cell dysfunction contributes to impaired antigen-specific humoral responses in sepsis-surviving mice

BAFF inhibition in SLE—Is tolerance restored?

Group 3 Innate Lymphoid Cells Exacerbate Lupus Nephritis by Promoting B Cell Activation in Kidney Ectopic Lymphoid Structures

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