Alloreactive humoral responses are one of the main causes of immune-mediated allograft injury in kidney transplantation. Different biological compartments are involved in the generation and maintenance of humoral alloreactivity through different specific B-cell subsets, showing a close interplay between them in order to orchestrate allograft rejection.

Methods: We investigated frequencies of HLA-specific (HLA-sp) memory B cells (mBc) both in peripheral blood and in bone marrow as well as Long Lived plasma cells (LLPC) residing in bone marrow in a group of healthy individuals (n=6), in highly sensitized patients awaiting for a kidney transplant (n=3) and in kidney transplant patients showing chronic humoral rejection (cABMR) with (n=4) or without circulating DSA (n=8). Comparison of HLA-sp mBc responses, antigen repertoire analyses of circulating antibodies as well as those obtained from mBc expanded cultures were investigated using a HLA B-cell ELISPOT assay and Luminex® platform, respectively.

Results: HLA-sp LLPC (CD138⁺) responses from bone marrow and circulating mBc frequencies were detectable in an important proportion of patients. All highly sensitized patients showed HLA-sp responses from both compartments. Most patients showed circulating HLA-sp mBc frequencies, regardless detectable circulating DSA. All cABMR patients without detectable DSA showed HLA-sp mBc frequencies in the periphery. Conversely, cABMR patients with detectable DSA displayed HLA-sp frequencies from either circulating mBc or LLPC. When we performed a 6 days polyclonal stimulation within the CD138^– fraction in bone marrow aspirates, an ASC-like phenotype (CD20^lowCD27^–CD38⁺⁺IgD^–) appeared in some patients showing the same antigen-specific repertoire than that observed in peripheral blood, suggesting a replenishment mechanism between both compartments.

Conclusion: Different functional B-cell subsets residing in different compartments seem to be responsible for the production and maintenance of circulating HLA-sp Ab thus, having key implications regarding treatment decision-making in kidney transplant patients developing chronic ABMR.

CITATION INFORMATION: Luque S, Lúcia M, Jarque M, Crespo E, Melilli E, Martorell J, Cruzado J, Torras J, Grinyó J, Bestard O. Biological Interplay Between Circulating HLA-sp Alloreactive Memory B-Cells and Long-Lived Plasma Cells in Kidney Transplant Patients Undergoing Chronic ABMR. Am J Transplant. 2017;17 (suppl 3).

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