How the immune system chooses antibodies – core paradigm: Among classic theories of antibody production, which one is the most widely accepted to explain specificity and expansion of antigen-reactive lymphocytes?

Introduction / Context:
The immune system’s ability to recognize an enormous diversity of antigens rests on how lymphocyte receptors are generated and selected. Competing historical theories attempted to explain this phenomenon, but one framework remains the modern cornerstone of immunology.

Given Data / Assumptions:

• Lymphocytes bear unique receptors generated before antigen exposure.
• Antigen selects preexisting clones to proliferate and differentiate.
• Memory and specificity arise from expansion of selected clones.

Concept / Approach:
Clonal selection theory posits that each lymphocyte has a single specificity. Upon encountering its cognate antigen, that clone proliferates and differentiates into effector and memory cells. This model explains primary and secondary responses, self-tolerance mechanisms (deletion of self-reactive clones), and affinity maturation when coupled with somatic hypermutation and selection in germinal centers.

Step-by-Step Solution:
List candidate theories and assess against modern data. Recognize that template/side-chain ideas conflict with pre-formed receptor diversity. Choose the model consistent with V(D)J recombination and clonal expansion. Select clonal selection theory.

Verification / Alternative check:
Molecular findings (V(D)J recombination, junctional diversity, somatic hypermutation) validate preexisting receptor diversity and antigen-driven clone expansion, aligning with clonal selection.

Why Other Options Are Wrong:
Side-chain and template theories propose antigen instructs receptor shape, which is inconsistent with genetic generation of receptor repertoires.

Common Pitfalls:
Assuming affinity maturation contradicts clonal selection; in reality, selection acts on mutations generated during germinal center reactions.

Final Answer:
Clonal selection theory.