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Clonal selection hypothesis often defined by four basic principles of which first two are

  1. Each lymphocyte bears a single type of receptor with a unique specificity.

  2. Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with a high affinity leads to lymphocyte activation.

If 1) is true and lymphocytes are differentiated to respond only to a specific antigen, the quanitity of lympocytes for a given antigen must be as low as total lympocytes / total antigen receptors. For 2) to happen, the very rare lymphocytes for an antigen must physically touch the antigen.

How is 2) achieved, assuming that 1) is true, and probability theory is a thing?

Edit: This question was heavily critiqued but once more, maybe the reason for that is the wrong reason. What Zhi said in 2019 perfectly reflects my own thoughts about the usual model of immunology, However, one B cell producing only one specific antibody would be unlikely to rapidly find its matching antigen. I do not mind the occassional random person I do not know projecting their prejudice on me, but, again, maybe done for wrong reason?

Shi, Z., Zhang, Q., Yan, H. et al. More than one antibody of individual B cells revealed by single-cell immune profiling. Cell Discov 5, 64 (2019). https://doi.org/10.1038/s41421-019-0137-3

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    $\begingroup$ Welcome to SE Biology. Please finish reading the tour and consult the help on asking questions. You will see that you need to give evidence that you have tried to answer this question yourself. What texts have you consulted? What you state about the theory (now fact) is incorrect. Each lymphocyte does not “only respond to one antigen”, it only responds to antigens that can bind to its receptor — hence polyclonal antibodies. And if you think something is statistically improbable, you need to present an argument that is at least partly numerical. $\endgroup$
    – David
    Aug 16, 2020 at 21:56

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This is the role of antigen-presenting cells, which are in charge of carrying samples of antigens to the secondary lymphoid organs (lymph nodes, spleen) where lymphocytes live. Once activated, B and T cells can activate each other through B-cell presentation and T-cell dependent activation.

It's also important that, for B-cells, the anti-body that they produce is still modified during clonal expansion through affinity maturation. This is essentially very fast mutation and selection that fine-tunes the antibody. So, there doesn't have to be an exact match to begin with, just a reasonably good one that will be improved during expansion.

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  • $\begingroup$ Thanks. Exact information transmission in immune system is very fascinating. Similar to peer-to-peer networks in computer science, for how two nodes find one another, which is a very hard problem still being worked on. Jerne's original work called it "the immune network". $\endgroup$
    – Pakim
    Aug 17, 2020 at 11:59
  • $\begingroup$ If antibodies as "packages" exist in 10^17 per milliliter serum, and they can magically connect antigen with lymphocyte through a sophisticated information relyaing mechanism, maybe similar approach can be used for P2P networks actually. $\endgroup$
    – Pakim
    Aug 17, 2020 at 12:00
  • $\begingroup$ Actually major difference in p2p network is "antigen" wants to be known. So, query flooding requests are likely exactly analogous to antibodies in how they're already being used. $\endgroup$
    – Pakim
    Aug 17, 2020 at 12:27

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