What are plasma cells?

What Are Plasma Cells?

Plasma cells are specialized, terminally differentiated B lymphocytes that constitutively synthesize and secrete antibodies to maintain humoral immunity. 1, 2

Cellular Characteristics and Morphology

Plasma cells have distinctive morphological features that allow their identification:

• Round or oval shape with characteristic basophilic cytoplasm and an eccentric nucleus containing coarse heterochromatin (often described as a "clock-face" pattern) 3, 4
• Pale perinuclear cytoplasmic crescent due to the prominent Golgi apparatus 3
• Lack surface immunoglobulin expression when fully mature, distinguishing them from their B cell precursors 4

Immunophenotype and Identification

Plasma cells can be reliably identified through specific surface markers:

• Co-expression of CD138 and CD38 is the hallmark for identifying plasma cells in flow cytometry from bone marrow, peripheral blood, or tissue suspensions 4
• Do not express CD20 antigen, making them resistant to CD20-targeted therapies like rituximab 3
• Additional markers may include variable expression of CD19, CD56, CD117, and HLA-DR depending on the clinical context 3

Functional Biology

Antibody Production

• Plasma cells are the primary source of antibody production in the body, representing the effector arm of humoral immunity 3, 1
• They constitutively secrete antibodies without requiring further antigenic stimulation 2

Lifespan Heterogeneity

Plasma cells exist in two functionally distinct populations:

• Short-lived plasmablasts and plasma cells that survive only as long as B cells remain activated (days to weeks), responding to immunosuppressive drugs and causing disease flares 1, 5
• Long-lived memory plasma cells that survive in specialized niches in bone marrow and inflamed tissues for months, years, or a lifetime, independent of B cell, T cell help, or antigen contact 1, 5, 6

Anatomical Location and Survival Niches

• Plasma cells primarily reside in bone marrow and lymphoid tissues where specialized microenvironmental niches support their survival 6
• The spleen houses antibody-producing plasma cells, serving as a reservoir for these cells 3
• Long-lived plasma cells also persist in inflamed tissues where local factors promote their retention 1, 6

Clinical Significance

Protective Role

• Plasma cells secreting protective antibodies against pathogens are crucial for immunological memory and vaccine efficacy 2, 6
• The longevity of plasma cells is the primary determinant of the duration of humoral immunity 2

Pathogenic Role

Dysregulated plasma cells contribute to multiple disease states:

• Autoimmune disorders through production of pathogenic autoantibodies (lupus, rheumatoid arthritis, multiple sclerosis) 1, 5, 6
• Transplant rejection via antibody-mediated mechanisms 1
• Allergic diseases through IgE production 1, 5
• Multiple myeloma representing malignant transformation of plasma cells 2, 5
• Plasma cell leukemia when malignant plasma cells circulate in peripheral blood (≥20% circulating plasma cells and/or absolute count >2×10⁹/L) 3, 7

Therapeutic Implications

Resistance to Standard Therapies

• Long-lived plasma cells are refractory to conventional immunosuppressants and B cell-depleting therapies (like rituximab) because they lack CD20 and do not require ongoing B cell support 3, 1, 5
• This resistance makes them responsible for therapy-resistant autoantibodies in chronic autoimmune conditions 1, 5

Targeting Strategies

• Proteasome inhibitors (bortezomib, carfilzomib) can effectively deplete plasma cells by disrupting their high protein synthesis machinery 3, 1
• Immunoablative therapy with antithymocyte globulin in stem cell transplantation settings can eliminate long-lived plasma cells 1
• Plasma cell survival depends on metabolic pathways, particularly glucose uptake and catabolism, representing potential therapeutic targets 2

Historical Context

The term "plasma cell" was introduced by anatomist Heinrich H. von Hartz-Waldeyer in 1875, though their role as antibody producers was discovered later and became a key finding that enabled the development of monoclonal antibodies 4