B- and T-cell memory

Definitions & Key takeaways

B and T cells are the two main types of lymphocytes or white blood cells that play a role in the immune response. Both B and T cells can remember previous encounters with foreign antigens, which helps them to quickly and effectively respond to future infections by the same microorganisms.

B cells produce antibodies, which bind to pathogens and mark them for destruction by other immune cells. T cells kill infected host cells or help B cells produce more antibodies. Memory B and T cells persist in the body for many years, providing lifelong protection against reinfection by the same pathogen.

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Your immune system is like the military - with two main branches, the innate immune response and the adaptive immune response.
Key features of the innate immune response are that the cells are non-specific, meaning that they don’t distinguish one invader from another invader, the response is really fast - occurring within minutes to hours, and there’s no memory associated with innate responses.
The adaptive response, which is mediated by lymphocytes like B and T cells - is the opposite of the innate immune response.
B and T cells have unique receptors - the B cell receptor and T cell receptor - that differentiate pathogens from each other using their unique parts - called antigens.
These receptors are developed while the T cell or B cell is developing in the bone marrow for B cells or thymus for T cells.
Once the cell has a unique antigen-specific receptor expressed on its surface it begins traveling through the lymphatic system - passing through lymph nodes in search for the one antigen that fits the receptor perfectly.
If they encounter that antigen, a signal gets delivered to the cell’s nucleus that lead to clonal expansion. That’s where a single T cell or B cell replicates over and over - creating an army of clones that can combat the pathogen.
Once the immune response is complete, many of these cells die by apoptosis restoring the immune response to its original size - with one major change.
Some of the B and T cells become memory cells, which are basically a pool of lymphocytes that are all set to combat the pathogen, if they encounter it again!
Immunologic memory is sometimes referred to as a secondary or anamnestic response, and it’s different from the primary response.
During the primary response a small number of naive B and T cells require activation before they can respond to the pathogen.
And activating those B and T cells requires a relatively high pathogen burden and can take days to weeks. And the innate response is really important to fill the gap while the adaptive response is being mounted.
In the secondary response, the memory B and T cells, as well as antibodies, are already made, and it takes a relatively low pathogen burden to re-engage the adaptive immune response.
As a result, the innate and adaptive immune response end up working with each other right away to eliminate the pathogen.
In the primary immune response, B cells get activated through their interactions with other immune cells. First, special dendritic cells called follicular dendritic cells trap antigens for the B cells and send out stimulatory cytokines.
Then, the B cell acts as an antigen presenting cell - serving up antigen to T follicular helper cells. In response, the T follicular helper cell expresses CD40L on its surface and produces IL-21, and together they induce the B cell undergo class switching.
In class switching, the B cell shifts from expressing a B cell receptor with IgM and IgD to expressing IgG, IgE, or IgA.
Some of these B cells that go on to become memory B cells. That means that are the memory response is limited to peptide antigens which can be seen by T cells.
And that T cell-independent antigens like lipids and carbohydrates don’t lead to memory B cells. It also means memory B cells don’t produce IgM and IgD.
Memory B cells live for up to 10 years in a lymph node, and they often differentiate into IgG secreting plasma cells when they get reactivated.
Now, because of somatic hypermutation, IgG antibodies created toward the end of the primary immune response typically have higher affinity than the IgM antibodies created early in the primary immune response.
These high affinity IgG antibodies therefore bind to Fc gamma receptor II on newly activated IgM producing B cells, inhibiting them from differentiating into plasma cells.
The result is that low affinity IgM production is halted, and high affinity IgG production from memory B cells is promoted.
The primary immune response, leads to the formation of lots of short-lived effector cells as well as a few long-lived memory cells.
When a T cell is first made, it expresses high levels of IL-7 receptor. For most T cells that become activated, IL-7 receptor levels decrease, and IL-2 receptor levels increase.
Think of IL-7 as nutritious vegetables and grains, and IL-2 as fast food. IL-2 is plentiful during the immune response, so the short-lived effector cells are able to work hard, but then die out once the immune response ends.
But a minority of T cells, maintain high levels of IL-7 receptors - and they’re able to survive even after the immune response ends.
These cells continue to live for years on their healthy diet of IL-7 which is generated by a variety of cells throughout the body including stromal cells in the bone marrow and thymus, keratinocytes, dendritic cells, hepatocytes, and epithelial cells.
In fact, the only cells that don’t seem to produce IL-7 are other lymphocytes. The cell surface ligand CD45 is helpful in identifying the various types of T cells.
The ligand undergoes alternative splicing which results in different versions of the protein - called CD45RA and CD45RO.
CD45RA, which has an “A” has all of its subunits and is expressed on naive T cells - naive with an “A”. CD45RO, which has an “O”, is a smaller protein because all of its exons are cleaved out and it’s expressed on memory and effector cells - both of which have an “O”.
Now, there are two types of T memory cells - central memory T cells and effector memory T cells. Central memory cells can live for up to 25 years and remain in the lymphoid tissue.
If they get reactivated by their antigen, they proliferate and create new effector T cells. In contrast, effector memory T cells, are able to move around the body looking for the pathogen.
If an effector memory cell encounters its pathogen it will respond just as it did in the primary immune response. For CD4+ helper T cells this means secreting cytokines to support the functions of the other immune cells.
For CD8+ cytotoxic T cells, this means binding to its antigen as it’s presented on a MHC class I molecule of a target cell, and destroying that target cell.
Alright, as a quick recap. The secondary immune response involves memory B and T cells that are created during the primary immune response.
Memory B cells are made as a result of signals from T follicular helper cells and follicular dendritic cells. These cells have already undergone class switching so they most often produce IgG, and sometimes IgA or IgE depending on the tissue, last for approximately 10 years, and largely remain in the lymph node.
Memory T cells survive after an immune response is over because they have IL-7 receptors, living up to 25 years. There are two types of memory T cells, both express the molecule CD45RO.
Effector memory cells travel in and out of the tissues and are able to directly respond to the pathogen if they see it. Central memory cells remain in lymphoid tissue where they can rapidly proliferate to create a pool of T cells to respond to the pathogen.