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#myeloma

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Immunological Applications

The main purpose of using myeloma cells in hybridoma technology is:

Primary plasma cells cannot be cultured long term because they activate intrinsic mitochondrial apoptosis via Bim upregulation when removed from survival niche provided by stromal cell contact, interleukin-6, and BAFF, plus replicative senescence triggered by telomere shortening each division. Myeloma cells circumvent these barriers through multiple oncogenic lesions: expression of hTERT telomerase reverse transcriptase adding TTAGGG repeats preventing crisis, disruption of p53-MDM2 axis, loss of cyclin dependent kinase inhibitors p16 and p21, autocrine loops via IGF-1 and interleukin-6 constitutively activating JAK-STAT3, and anti-apoptotic proteins Bcl-2, Mcl-1, Bcl-xL sequestering Bax-Bak. Metabolically they exhibit enhanced aerobic glycolysis and glutaminolysis supporting high rate immunoglobulin synthesis of 20 to 50 picograms per cell per day needed for commercial manufacture. Specificity remains encoded entirely by B cell derived VDJ sequences while unlimited division derives solely from tumor genome. Without immortality contribution, antibody secreting clones exhaust after few doublings, master cell banking for regulatory filing impossible, and large-scale therapeutic production economically unfeasible, underscoring myeloma purpose for perpetuating culture.

Ref: Freshney Culture Animal Cells 7th ed myeloma immortality hTERT; Abbas Cellular Molecular Immunology hybridoma immortalization.

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Immunological Applications

The main purpose of using myeloma cells in hybridoma technology is:

Primary B lymphocytes after differentiation short-lived plasma cells produce Ig extraordinary rate but survive 3-5 days culture due activation-induced death mediated Fas upregulation after strong BCR crosslinking and lack telomere maintenance somatic cells lacking telomerase entering senescence limited divisions dependence extrinsic survival signals CD40L helper T cells cytokines IL-4 IL-6 IL-21 follicular helper. Continuous monoclonal manufacturing over months requires immortalization essential. Myeloma plasmacytoma malignant transformation plasma cells proliferate indefinitely without exogenous growth factors due translocation placing oncogene c-myc under IgH enhancer driving cyclin D and constitutive IL-6 secretion creating autocrine loop activating JAK-STAT pathway promoting survival proliferation. Fusion with B cell transfers transformation phenotype granting hybridoma sustained division >100 passages cryopreservation stability preserving viability liquid nitrogen storage ability grow serum-free chemically defined bioreactors scaled 2000 L robust ER comprising chaperone BiP protein disulfide isomerase folding heavy light chains efficiently. While antibody specificity derives entirely B-cell partner rearranged Ig loci longevity continuous secretion originate myeloma component overcoming natural mortality limitation enabling long-term production and banking hybridoma lines.

Ref: Kohler Milstein Myeloma Immortality Principle 1975; Lodish Hybridoma Immortalization Mechanism Biology; Janeway Myeloma Fusion Purpose Immunobiology Chapter 2.

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