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THU0034 CD19 Distinguishes Memory and Pre-Memory Antibody Secreting Cells
  1. R. Herbst1,
  2. B. Rajan1,
  3. C. A. Morehouse1,
  4. R. Rayanki1,
  5. Y. Yao1,
  6. R. Ettinger1,
  7. Y. Wang1,
  8. C. J. Groves1
  1. 1Research, MedImmune LLC, Gaithersburg, United States

Abstract

Background Plasma cells (PC), are differentiated B cells that play a major role in humoral immunity as they actively secrete antibodies which identify and neutralize foreign antigens. Normally, plasma cells develop in response to immune challenges such as infection or vaccination. In autoimmune diseases, however, PCs develop which secrete anti-self antibodies that may play a role in disease pathogenesis. Therefore, PCs are potential targets for therapeutic intervention in autoimmune disease. However, consideration must be given to the potential impact on protective immunity of PC targeted therapy.

Objectives A recent report has identified long-lived PC in autoimmune patients which secrete Ig specific for self-antigen (1). These autoreactive cells represent a novel therapeutic target. The self-reactive PCs in the study were identified by commonly known cellular markers including the surface expression of CD19. CD19 is a molecule that is present on B cells from the earliest stages of development through the memory and plasma cell stage. Therefore, our goal was to characterize in detail the expression of CD19 on plasmablasts and plasma cells from human blood and tissues, and relate the phenotype of PCs from different tissues to production of antigen-specific immunoglobulin.

Methods PCs were isolated from peripheral blood, tonsil, spleen, and bone marrow (BM) from human donors and characterized for surface antigen expression by flow cytometry. Samples of sorted cells were further characterized by mRNA expression profiling and by ELISPOT to determine total as well as antigen-specific production of immunoglobulin.

Results Here we show that CD19 is expressed on normal PC found in human blood, tonsil, spleen, and bone marrow. However, we have identified a population of CD19- PC which exists in the spleen and bone marrow as a sub-population of PC in these tissues. We show that the bone marrow CD19- PC and CD19+ PC have nearly identical morphology, immunophenotype, mRNA expression, and function. However the CD19- PC fraction has a significantly increased frequency of cels which secrete antibodies specific for tetanus/diptheria toxin and influenza vaccine antigens when compared to CD19+ PC in human BM.

Conclusions The results demonstrate that most PC from human blood and tissue are CD19+, although cell surface levels of CD19 can vary. Importantly, there exists a distinct CD19- population of PC in spleen and BM. These cells appear to be of a long-lived memory phenotype and secrete antibodies to vaccine antigens. The results have significant implications for the targeting of PC in autoimmune disease, especially with depleting antibodies against CD19, such as MEDI-551.

References

  1. Mahévas M. et al (2013) B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells. J Clin Invest 123(1):432-42.

Disclosure of Interest None Declared

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