A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow

Abstract

Key Points Healthy human BM is enriched for PC lacking CD19 that express a prosurvival and distinctly mature phenotype. CD19− PC resist mobilization into blood during immune responses after vaccination as well as B-cell depletion with rituximab.

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“…8,10 In contrast to regenerating activated CD20+ B cells, SLMPCs and mainly LLMPCs (nonproliferating B cells niched in the bone marrow and inflamed organs), which produce considerable amounts of IgG autoantibodies and alloantibodies, lack both CD20 and CD19 markers. [5][6][7] Consequently, these cells would be resistant to in vivo B-cell depletion by anti-CD20 MAb therapies, as recently reported in patients with rheumatoid arthritis 6 and in patients with iMGN. 8 This may explain the frequently observed relapses or primary resistance of patients with iMGN to anti-CD20 therapy despite ongoing B-cell depletion defined by eradication of CD19+ and CD20+ cells.…”

“…5,6 As expected, LLMPCs that lack CD20 markers [5][6][7] would be refractory to a CD20+-targeting immunosuppressive therapy (Figure 1). 6 This may partly explain the limited rate of complete remission (which does not exceed 20% in all treated patients) and the rates of relapse, partial response, or no response (nearly 80% of all patients) observed in most studies using the anti-CD20 MAb rituximab, as rescue or a firstline therapy in native iMGN. This was recently shown in the French GEMRITUX trial 8 and in a large observational study involving 132 patients.…”

“…The non-proliferating LLMPCs are known to provide the basis for humoral memory and refractory autoimmune diseases. [5][6][7][8][9] Recent evidence has suggested the existence of 2 independent plasma cell (CD19+/CD20+ and CD38+/CD138+) compartments that contribute to autoantibody and alloantibody production. 5,6 As expected, LLMPCs that lack CD20 markers [5][6][7] would be refractory to a CD20+-targeting immunosuppressive therapy (Figure 1).…”

“…[5][6][7][8][9] Recent evidence has suggested the existence of 2 independent plasma cell (CD19+/CD20+ and CD38+/CD138+) compartments that contribute to autoantibody and alloantibody production. 5,6 As expected, LLMPCs that lack CD20 markers [5][6][7] would be refractory to a CD20+-targeting immunosuppressive therapy (Figure 1). 6 This may partly explain the limited rate of complete remission (which does not exceed 20% in all treated patients) and the rates of relapse, partial response, or no response (nearly 80% of all patients) observed in most studies using the anti-CD20 MAb rituximab, as rescue or a firstline therapy in native iMGN.…”

“…These preliminary observations indicated that different B-cell subtypes play a central role in the immunopathogenesis of recurrent posttransplant iMGN involving CD20+-activated B cells and CD19-/CD20-/CD38+/CD138+ LLMPCs, belonging to 2 separate compartments. [4][5][6][7] The LLMPC autoreactive or alloreactive B cells produce autoantibodies and alloantibodies in an independent fashion from the activated CD20+ B cells. They are refractory to conventional immunosuppressive drugs and to therapeutic approaches that target CD20+ B cells 6 and may be partially depleted by the PI bortezomib.…”