I've just learned about B cells in immunology lectures and some things are not clear to me.

Here's what I know:

1) Apparently, each B cell produces a specific antibody, determined randomly at the birth of that cell.

2) A B-cell expresses 250000 different antibodies on its surface

My question:

Are both these facts true? If so, how can they both be true if each B cell only produces a single specific antibody?

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    $\begingroup$ The specificity of antibodies is answered below. However, I think the answerer misunderstood the "250000" number. What this actually refers to is the number of copies of the cell's antibody that are on the cell surface - each antibody-producing B cell has approximately 250000 antibody molecules on its surface. Each one of those copies is identical, all recognizing exactly the same epitope. $\endgroup$ – MattDMo Apr 25 '16 at 22:03

Statement 1 is true and Statement 2, false.

B cells, in the absence of antigenic stimulation express surface receptors(B-cell receptors or BCRs), which look like normal secreted antibodies (but these are membrane bound and not secreted). What is amazing is that each B cell at a particular time expresses the same B cell receptor - same as in, all receptors produced off one B cell are of the same type, say, antigen A. Now, another B cell produces another type of receptors, say, those which detect Antigen B. There is not just one BCR on the B-cell, but many - just like any other cellular receptor.

Now, there are many B cells in the body. Very much like antigen A and antigen B, there so many more antigens that our body can produce antibodies against. (The source I quote below says $\ 10^{12} $) It is a wrong notion that just one little B cell is doing that all. There are specific B cells for each specific antibody.

Each B cell isn't necessarily producing a unique antibody, but yeah, specific. It isn't unique since there must be a few more similar B cells producing the same receptor against antigen A. So it is not just one single B cell producing antibody against 'A'.

How does the body produce so many types of specific proteins?

Being proteins, they must be encoded by genes. B-cells while maturing, undergo a recombination (shuffling) of their immunoglobulin genes which leads to this differential expression of receptors, hence the diversity.

For further reading on genetics of immunoglobulins and the generation of diversity, I'd suggest - http://www.ncbi.nlm.nih.gov/books/NBK26860/

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  • $\begingroup$ Also important to note is that there is significant antibody cross reaction with related antigens which makes the defense even more formidable! $\endgroup$ – Polisetty Apr 25 '16 at 16:37
  • $\begingroup$ Please see my comment above. Statement 2 is true, you just misunderstood the question. $\endgroup$ – MattDMo Apr 25 '16 at 22:08
  • $\begingroup$ @MattDmo the questions says, "250000 different". As you said, they arent different, but recognize the same epitope. The number meant something different, ill edit it in the answer! So statement 2 still remains false anyway for the 'different' part. $\endgroup$ – Polisetty Apr 26 '16 at 15:32
  • $\begingroup$ I'm not sure how "different" got in there, I suspect it may be a translation issue or something similar. I suppose the BCRs are "different" in that they're different individual molecules, perhaps what the OP meant to say. I don't know... :) $\endgroup$ – MattDMo Apr 26 '16 at 16:57
  • $\begingroup$ @MattDMo true that! :D Maybe that's what different meant!! I have edited the answer, but anyway could you pls paste a reference regarding the 250000. Like, the number of receptors expressed on the cell. $\endgroup$ – Polisetty Apr 26 '16 at 17:05

Statement 1 is true. Statement 2 is false.

My explanation is from the perspective of immune cell development:

The antibody-producing B cells are called plasma B cells. Plasma B cells are differentiated from a single naïve B cell (undifferentiated B cell). The naïve B cell have all the cell structure. However, naïve B cell can also be differentiated into memory B cells. When one single B cells receives differentiation signals from a T helper cell and differentiate into a plasma B cell, it grows bigger and starts proliferation. Thus you end up with many plasma B cells all coming from the same very first plasma B cell differentiated of this type. So one type of plasma B cells MUST present the SAME type of receptors on their surfaces.

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Primary Reference: Cellular and Molecular Immunology, 8th ED.

Statement 1 is only part true. B cells produce b cell receptors of a specific paratope, that are randomly determined during maturation. The process of V(d)j recombination, where productive rearrangements in the heavy chain and light chain genes, produces a primary CHtranscript consisting of V-D-J-Cµ-Cδ. Enzymes in the matured B cell can differentially process the H-chain transcript into VDJ-Cµ or VDJ-Cδ which confer IgM or IgD-isotype BCRs. Mind you, during recombination and rearrangement, the extra DNA is deleted that would otherwise lead to other receptor possibilities, and signals are activated that prevent any potential recombination from taking place on another chromosome. This maintains a single antigen specificity on all clones of a given B cell!

The only difference between a BCR and an antibody produced by that B cell is the presence of a C-terminal membrane anchor region. How the protein is processed is determined by what proteins are processing the primary mRNA.

B cells retain in their DNA C regions for other heavy chains, however. In the presence of certain costimulatory signals, they can class switch to a different isotype that retains the paratope of the B cell. I explain this at length here.

I want to stress here that only the paratope or antigen-binding site is maintained, and B cells can produce a number of different isotypes of BCR or secreted antibody (though class switching is generally irreversible).

Statement 2 follows that due to the above statement, a B cell cannot express 250,000 different BCRs. Rather, they express one paratope across different isotypes. While I don't have the data in front of me, 250,000 may very well refer to surface density of BCRs on a given B cell.

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