Plasma cells and antibodies

Plasmocyte Morphology and Life Cycle

A plasmocyte is a large cell, over 20 µm in size. Its distinctive features are a huge basophilic cytoplasm and characteristic chromatin condensation at the periphery of the nucleus. Since the cell is a protein "factory," it features a heavily developed rough endoplasmic reticulum and Golgi apparatus. Mature forms completely lose the ability to divide.

Cell lifespan directly depends on formation conditions and habitat:

• Short-lived (5–7 days): form in vitro or under suboptimal conditions (e.g., outside germinal centers).
• Medium-lived (4–7 weeks): typical for the spleen and lymph nodes.
• Long-lived (decades): make up 10–20% of the pool and form lifelong immunity. For survival, they migrate to the bone marrow or foci of inflammation. Their viability is maintained by constant contact with stromal cells, the chemokine CXCL12 (SDF-1) binding to the CXCR4 receptor, surface molecules (CD138, CD44, LFA-1), and intracellular factors (Bcl-1, Blimp-1).

Synthesis, Assembly, and Isotype Switching

Antibody production obeys a strict rule: a single cell secretes antibodies of only one specificity (matching the receptor of the original B cell), one isotype, and allotype.

The transition of the molecule from the membrane-bound form to the secreted form is ensured by heavy chain mRNA splicing. Regions encoding the membrane domain (MC exons) are removed, and instead, the SC exon responsible for the soluble C-terminal part is expressed. The soluble form loses the ability to embed in the membrane and is secreted outward through the Golgi apparatus.

The isotype switching process is controlled by cytokines:

• With the participation of IL-2, IL-4, IL-5 (without switching), cells secreting IgM are formed. Their peak in serum occurs rapidly—on days 5–6.
• Under the influence of IL-4, switching to IgG1 and IgE occurs. The IgG peak occurs later (days 10–12), but the high titer persists for weeks.
• The action of IFNγ leads to the synthesis of IgG2a/3, while TGFα induces IgA and IgG2b.

Immunoglobulin assembly proceeds via two pathways. IgG is characterized by the dimerization of heavy chains ($H + H \rightarrow H_2$), to which light chains are sequentially attached ($H_2 + L \rightarrow H_2L \rightarrow H_2L_2$). For IgM, a mixed dimer ($H + L \rightarrow HL$) is formed first, and only then two such blocks combine.

Effector Mechanisms of Antibodies

Antibodies act both independently and as "targeting agents" for innate immunity factors. There are 4 main mechanisms:

1. Direct neutralization and blockade. Antibodies spatially shield toxins or microbial surface structures. This is the main function of IgA on mucous membranes, as well as the IgG2 and IgG4 subclasses. Toxin neutralization forms the basis of serotherapy (e.g., in tetanus).
2. Opsonization for phagocytes. Antibodies (especially IgG1 and IgG3) coat the target, greatly facilitating its capture by macrophages.
3. Antibody-dependent cellular cytotoxicity (ADCC). Target-bound antibodies are recognized by the FcγRIII (CD16) receptor on the surface of NK cells. This triggers direct contact cytolysis of tumor or infected cells.
4. Complement activation. Upon immune complex formation, the antibody molecule changes conformation, exposing the $C_H2$ and $C_H3$ domains. The C1q protein binds to them, initiating the classical complement pathway. The result is massive deposition of C3b opsonins on the target, which is much more important for defense than direct lytic complement action.

Hybridomas: Monoclonal Antibody Factories

To obtain monoclonal antibodies of a given specificity, a technology created in 1976 by G. Köhler and C. Milstein is used.

Its essence lies in the somatic hybridization of two different cell types:

• Antibody-producing cell (taken from the spleen of an immunized mouse) — it transfers the ability to produce the desired antibody to the hybrid.
• Myeloma (tumor) cell — it provides the ability for infinite division outside the body.

Initially, Sendai virus was used for membrane fusion; today, polyethylene glycol, combining hydrophilic and hydrophobic groups, has become the standard. The resulting hybridoma cell serves as a continuous source of absolutely identical immunoglobulin molecules.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Detailed mechanisms of DNA-level isotype switching and the role of T-helper cells.
• Features of complement system activation by antibodies of different classes.
• Interaction of plasmocytes with the bone marrow niche: the role of CD138 molecules and chemokines.
• Differences in antibody production kinetics during primary and secondary immune responses.

Other topics in the "Adaptive Immunity" section

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