B Cells and T Cells

The bone marrow produces all the blood cells: red blood cells, white blood cells (also called leukocytes), and platelets. The most abundant of the white blood cells are the lymphocytes.

• B lymphocytes (often simply called B cells) and
• T lymphocytes (likewise called T cells)

Each B cell and T cell is specific for a particular antigen. What this means is that each is able to recognize and bind to a particular molecular structure.

The specificity of binding resides in a receptor for antigen:

• the B cell receptor (BCR) for antigen and
• the T cell receptor (TCR) respectively.

• they are integral membrane proteins
• they are present in thousands of identical copies exposed at the cell surface
• they are made before the cell ever encounters an antigen
• they are encoded by genes assembled by the recombination of segments of DNA

  How antigen receptor diversity is generated

• they have a unique binding site
• this site binds to a portion of the antigen called an antigenic determinant or epitope
• the binding, like that between an enzyme and its substrate depends on complementarity of the surface of the receptor and the surface of the epitope
• the binding occurs by non-covalent forces (again, like an enzyme binding to its substrate)
• successful binding of the antigen receptor to the epitope, if accompanied by additional "signals", results in:
  • stimulation of the cell to leave G₀ and enter the cell cycle
  • repeated mitosis leads to the development of a clone of cells bearing the same antigen receptor; that is, a clone of cells of the identical specificity.

• their structure
• the genes that encode them
• the type of epitope to which they bind

B Cells

• BCRs bind soluble antigens (like diphtheria toxoid, the protein introduced into your body in the DTP vaccine)
• the bound antigen molecules are engulfed into the B cell by receptor-mediated endocytosis
• the antigen is digested into fragments which
• are then displayed at the cell surface nestled inside a class II histocompatibility molecule
• Helper T cells specific for this structure (i.e., with complementary TCRs) bind the B cell and
• secrete lymphokines that:
  • stimulate the B cell to enter the cell cycle and develop, by repeated mitosis, into a clone of cells with identical BCRs
  • switch from synthesizing their BCRs as integral membrane proteins to a soluble version
  • differentiate into plasma cells that secrete these soluble BCRs, which we now call antibodies.

T Cells

• a fragment of an antigen lying within the groove of a
• histocompatibility molecule

The complex has been compared to a "hot dog in a bun".

• CD4
• CD8

• CD8⁺ T cells bind epitopes that are part of class I histocompatibility molecules. Almost all the cells of the body express class I molecules.
• CD4⁺ T cells bind epitopes that are part of class II histocompatibility molecules. Only specialized antigen-presenting cells express class II molecules. These include:
  • dendritic cells
  • phagocytic cells like macrophages and
  • B cells!

CD8⁺ T cells

The best understood CD8⁺ T cells are cytotoxic T lymphocytes (CTLs). They secrete molecules that destroy the cell to which they have bound. This is a very useful function if the target cell is infected with a virus because the cell is usually destroyed before it can release a fresh crop of viruses able to infect other cells.

An example will show the beauty and biological efficiency of this mechanism.

Every time you get a virus infection, say influenza (flu), the virus invades certain cells of your body (in this case cells of the respiratory passages). Once inside, the virus subverts the metabolism of the cell to make more virus. This involves synthesizing a number of different macromolecules encoded by the viral genome.

In due course, these are assembled into a fresh crop of virus particles that leave the cell (often killing it in the process) and spread to new target cells.

Except while in transit from their old homes to their new, the viruses work inside of your cells safe from any antibodies that might be present in blood, lymph, and secretions.

But early in the process, infected cells display fragments of the viral proteins in their surface class I molecules. CTLs specific for that antigen will be able to bind to the infected cell and often will be able to destroy it before it can release a fresh crop of viruses.

In general, the role of the CD8⁺ T cells is to monitor all the cells of the body, ready to destroy any that express foreign antigen fragments in their class I molecules.

CD4⁺ T cells

• cell-mediated immunity

  These CD4⁺ cells bind to antigen presented by antigen-presenting cells (APCs) like phagocytic macrophages and dendritic cells. The T cells then release lymphokines that attract other cells to the area. The result is inflammation: the accumulation of cells and molecules that attempt to wall off and destroy the antigenic material (an abscess is one example, the rash following exposure to poison ivy is another).

• antibody-mediated immunity

  These CD4⁺ cells, called helper T cells, bind to antigen presented by B cells (as shown above). The result is the development of clones of plasma cells secreting antibodies against the antigenic material.

  Link to a discussion of antigen-presenting cells.

  Link to a discussion of helper T cells.

AIDS patients lose their CD4⁺ T cells

AIDS provides a vivid and tragic illustration of the importance of CD4⁺ T cells in immunity. The human immunodeficiency virus (HIV) binds to CD4 molecules and thus is able to invade and infect CD4⁺ T cells. As the disease progresses, the number of CD4⁺ T cells declines below its normal level of about 1000 per microliter (µl). (A partial explanation for this may be the unceasing efforts of the patient's CD8⁺ T cells to destroy the infected CD4⁺ cells. However, it turns out that only a small fraction of the patients CD4⁺ T cells are infected at any given time. How uninfected CD4⁺ cells may be induced to commit suicide is discussed in the page on apoptosis.)

When the number of CD4⁺ T cells drops below 400 per microliter, the ability of the patient to mount an immune response declines dangerously. Not only does the patient become hypersusceptible to pathogens that give all of us grief but also to microorganisms, especially viruses and fungi, that normally inhabit our tissues without harming us. Eventually the patient dies of these opportunistic infections.