In situ identification of allospecific B cells using pentamers

Panoskaltsis‐Mortari, Angela; Taylor, Patricia A.; Riddle, Megan; Shlomchik, Mark A.; Blazar, Bruce R.

doi:10.1182/blood-2007-12-127415

Cited by 3 publications

(1 citation statement)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using MHC class I pentamers or tetramers reactive with donor splenocytes, we and Chen et al demonstrated the presence of pentamer/tetramer positive B cells in the GCs of spleen of the host (35,37). Such data, and those of Gilson and Zimring with platelet transfusion (31), may have suggested that splenectomized mice or mice that had been depleted of B cells should have reduced or rapidly waning alloantibody.…”

Section: Discussionmentioning

confidence: 60%

Strategies to Inhibit Alloantibody Production in Alloprimed Murine Recipients of Hematopoietic Stem Cell Grafts

Blazar¹,

Flynn²,

Lee

et al. 2015

American Journal of Transplantation

View full text Add to dashboard Cite

Alloantibody, not primed T cells, is the major barrier to bone marrow (BM) engraftment in allosensitized mice. We have shown that a single intravenous injection of donor splenocytes, to mimic a blood transfusion, results in high, sustained levels of serum alloantibody sufficient to eliminate donor BM within 3 h, resulting in uniform mortality in lethally irradiated allogeneic recipients. Current studies focused preventing and treating allopriming. Blockade of B cell survival signals with mTACI-Ig pre-and postpriming was ineffective, as was the B cell but not plasma cell depleting anti-CD20 mAb. Germinal center formation inhibition by lymphotoxin-beta receptor-Ig (LbR-Ig) diminished allosensitization, although conditional Prmd1 (Blimp-1) deletion in CD19þ cells was highly effective. By combining anti-CD20 mAb to reduce B cells and LTbR-Ig to diminish the frequency of B cells that could form germinal centers pre-and postpriming, allosensitization was precluded, permitting long-term survival in T-and NK-depleted, irradiated allogeneic recipients, whereas combined therapy postpriming alone was ineffective. As evidence of the critical role of B cells, the proteosomal inhibitor, bortezomib, given unencapsulated or encapsulated, proved ineffective in influencing allosensitization. These data extend our understanding of allopriming and provide a potential therapy for patients at risk for allosensitization and BM graft rejection.Abbreviations: APRIL, a proliferation-inducing ligand; BLIMP-1, B-lymphocyte induced maturation protein-1; BLyS, B-lymphocyte stimulator; BM, bone marrow; BMT, bone marrow transplantation; BTZ, bortezomib; Fl, flox; Ig, immunoglobulin; LTbR-Ig, lymphotoxinbeta receptor-immunoglobulin; MFI, mean fluorescent intensity; (m)TACI, (mouse) transmembrane activator and calcium-modulator and cyclophilin ligand receptor interactor; PB, peripheral blood; PBL, peripheral blood lymphocyte; PC, plasma cell; Prmd1, PR domain containing 1, with ZNF domain; Tfh, T follicular helper cell

show abstract

Section: Discussionmentioning

confidence: 60%

Strategies to Inhibit Alloantibody Production in Alloprimed Murine Recipients of Hematopoietic Stem Cell Grafts

Blazar¹,

Flynn²,

Lee

et al. 2015

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides

Huang,

Zhu,

et al. 2023

Nature

View full text Add to dashboard Cite

Reversing Endogenous Alloreactive B Cell GC Responses With Anti-CD154 or CTLA-4Ig

Chen

Yin

et al. 2013

American Journal of Transplantation

View full text Add to dashboard Cite

Alloantibodies mediate acute antibody-mediated rejection as well as chronic allograft rejection in clinical transplantation. To better understand the cellular dynamics driving antibody production, we focused on the activation and differentiation of alloreactive B cells in the draining lymph nodes and spleen following sensitization to allogeneic cells or hearts. We used a modified staining approach with a single MHC Class I tetramer (Kd) bound to two different fluorochromes to discriminate between the Class I-binding and fluorochrome-streptavidin-binding B cells with a high degree of specificity and binding efficiency. By day 7-8 post-sensitization, there was a 1.5-3.2-fold increase in the total numbers of Kd-binding B cells. Within this Kd-binding B cell population, approximately half were IgDlow, MHC Class IIhigh and CD86+, 30-45 % expressed a germinal center (Fas+GL7+) phenotype, and 3-12 % were IRF4hi plasma cells. Remarkably, blockade with anti-CD40 or CTLA-4Ig, starting on day 7 post-immunization for 1 or 4 weeks, completely dissolved established GCs and halted further development of the alloantibody response. Thus MHC Class I tetramers can specifically track the in vivo fate of endogenous, Class I-specific B cells, and was used to demonstrate the ability of delayed treatment with anti-CD154 and CTLA-4Ig to halt established allo-B cell responses.

show abstract

In situ identification of allospecific B cells using pentamers

Cited by 3 publications

References 5 publications

Strategies to Inhibit Alloantibody Production in Alloprimed Murine Recipients of Hematopoietic Stem Cell Grafts

Strategies to Inhibit Alloantibody Production in Alloprimed Murine Recipients of Hematopoietic Stem Cell Grafts

Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides

Reversing Endogenous Alloreactive B Cell GC Responses With Anti-CD154 or CTLA-4Ig

Contact Info

Product

Resources

About