1
$\begingroup$

This is a learning objective in my curriculum, and after having spent two hours trying to answer it for myself using official course resources (many of which are online, but some of which are behind paywalls and so may be inaccessible to other community members), it's clear to me that I need some assistance.

So I would just like to know what is the latest understanding of the major steps of follicular B cell development in mouse and human.

$\endgroup$
1
$\begingroup$

According to Basic Immunology - Functions and Disorders of the Immune System (3rd Ed.) by Abbas and Lichtman (Copyright © 2011 by Saunders), p.133:

A majority of B cells are called follicular B cells because they reside in the follicles of lymphoid organs. These follicular B cells make the bulk of T-dependent, class-switched, and high-affinity antibody responses to protein antigens and give rise to long-lived plasma cells.

and in the caption for FIGURE 7-2: image and caption use here is believed to be a fair use of copyrighted material

Subsets of B cells. Follicular B cells make T-dependent responses to protein antigens, and marginal zone and B-1 B cells account for most of the T-independent antibody responses. In mice it has been shown that B-1 B cells arise earlier in development, from progenitors in the fetal liver, and follicular and marginal zone B cells arise later, from bone marrow precursors. Comparable differences in the origins of these subsets have not been defined in humans. Note also that the distinctions in the type of response are not absolute—follicular B cells can make T-independent responses and marginal zone B cells can make some T-dependent responses. Ig, immunoglobulin.

(emphasis not in original)

From the sentence I emphasized, it seems to me that as of 02011, there is still a great deal that is not well-understood about the origins (and perhaps also development?) of human follicular B cells.

Interestingly, in the 4th edition of this textbook (Copyright © 2015 by Saunders), the details have changed slightly (as below):

image and caption use here is believed to be a fair use of copyrighted material

Subsets of B cells. Follicular B cells make T-dependent responses to protein antigens, and marginal-zone and B-1 cells account for most of the T-independent antibody responses. In mice, B-1 cells arise earlier in development, from progenitors in the fetal liver, and follicular and marginal-zone B cells arise later, from bone marrow precursors. Note also that the distinctions in the type of response are not absolute; follicular B cells can make T-independent responses, and marginal-zone B cells can make some T-dependent responses. Ig, Immunoglobulin.

Most interesting to me is the removal of the 3ed sentence: "Comparable differences in the origins of these subsets have not been defined in humans." Which leads me to believe that comparable differences in the origins of these subsets have now been defined in humans (in the past 4 years).

So I have a definition and description of follicular B cells, but I am unable to find anything else in either edition of this book on the development of follicular B cells (in either mouse or human).

Another reference in my course resources is Cellular and Molecular Immunology, 8th ed., 2014, by Abbas, Lichtman, and Pillai.

In it (Chapter 12: B cell activation and Antibody Production), I find the following about follicular B cells:

Distinct subsets of B cells respond preferentially to different types of antigens ( Fig. 12-3 ). Follicular B cells in peripheral lymphoid organs primarily make antibody responses to protein antigens that require collaboration with helper T cells.

Which strikes me as yet another description of follicular B cells, but not a list of steps in their development (which is my learning objective).

The same textbook makes several other mentions of follicular B cells, but does not address their development. Although I should probably already know this (and this may be in some of my lectures but these are not universally searchable and I have precious little time to read), I do not know about either their progenitors or their progeny, and I think this is what is meant by this learning objective: the major steps in their development.

In the same chapter of the same textbook, I also see:

Most mature naive B lymphocytes are follicular B cells (sometimes also called recirculating B cells) that constantly recirculate in the blood and migrate from one secondary lymphoid organ to the next in search of antigen. Follicular B cells enter secondary lymphoid tissues (spleen, lymph nodes, mucosal lymphoid tissues) through blood vessels located in the T cell zones, and then they migrate into the follicles, the B cell zones of these tissues. The movement into lymphoid follicles is guided by the chemokine CXCL13 secreted by follicular dendritic cells, the major stromal cell type in the follicle, as well as by other stromal cells. CXCL13 binds to the CXCR5 chemokine receptor on the recirculating naive B cells and attracts these cells into the follicles. As we will discuss later, the same chemokine-receptor pair is also important during immune responses because it can attract a subset of activated T cells to the follicle.

This seems like a great description of the follicular B cell that also delves into its function, but seems to include nothing about its development.

The same chapter of the same textbook also includes:

Naive follicular B cells survive for limited periods until they encounter antigen (see Chapter 2 ). Follicular B cell survival depends on signals from the BCR as well as on inputs received from a tumor necrosis factor (TNF) superfamily cytokine called BAFF (B cell–activating factor of the TNF family, also known as BLyS, for B lymphocyte stimulator), which provides maturation and survival signals through the BAFF receptor. BAFF and a related ligand, APRIL, can activate two other receptors, TACI and BCMA, which participate in later stages of B cell activation and differentiation (and will be discussed later). These cytokines are produced mainly by myeloid cells in lymphoid follicles and in the bone marrow.

This paragraph briefly address a little bit of what seems like the development of the follicular B cell ("Follicular B cell survival depends on..."). And in chapter 2 I see that follicular B cells are a class of B lymphocytes (along with Marginal zone B cells), but I interpret this learning objective as about the development of follicular B cells after they become follicular B cells, not before this point in their development.

So this is the best answer I can find on my own after many hours of searching and reading relevant passages in recent textbooks on the subject. Yet this answer also seems incomplete to me. After all this reading, I still have no "steps (per se) of follicular B cell development."

So I could really use a more complete answer.

$\endgroup$
  • 1
    $\begingroup$ Try Janeway's Immunobiology 8th edition, Chapter 10 The Humoral Immune Response. It is a bit too long to summarize in an answer here, but it should give you everything that you want to know about B-Cell development, maturation, and differentiation. $\endgroup$ – AMR Oct 4 '15 at 1:08
  • 1
    $\begingroup$ Very basically it is, migrate to secondary lymphoid organs, have antigen presented by follicular dendritic cells, migrate to boundary with T-cell area, (for simplicity) get activated by Helper T-cell, proliferate, migrate to red pulp (if the secondary lymphoid organ they were activated in was the spleen) and differentiate (or while differentiating) into a plasmablast, then terminally differentiate into antibody-secreting plasma cells, start pumping out Immunoglobulins and let the opsonization begin. $\endgroup$ – AMR Oct 4 '15 at 1:23
  • $\begingroup$ Thanks @AMR for this very helpful comment. I actually do have Janeway's so I'm looking at Chapter 10 now. But I'm not seeing what you described in your second comment. Do you have a page number or a section number? The caption for Fig. 10-7 talks some about this, but I don't see in Janeway that very comprehensive list of steps in the development of a follicular B cell that you listed. I'm in chat right now if you can spare the time to continue the conversation there. What are all the synonyms for "follicular B cell"? Not obvious to me. $\endgroup$ – Osteoboon Oct 4 '15 at 14:54
  • 1
    $\begingroup$ Section 10.5 beginning on 392. It is summarized in Figure 10.7 on page 394. I think that they are called follicular B cells for the simple reason that the area where they migrate to and are activated in secondary lymphoid organs is known as the B-cell Follicle. Biologist are nothing if not unoriginal... Except for fly geneticists... $\endgroup$ – AMR Oct 4 '15 at 15:03

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.