what cell type produces antibodies

B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules; however, these antibodies are not secreted. Rather, they are inserted into the plasma membrane where they serve as a part of B-cell receptors.

When a naïve or memory B cell is activated by an antigen, it proliferates and differentiates into an antibody-secreting effector cell, known as a plasmablast or plasma cell. Additionally, B cells present antigens (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines. In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, which is why the ‘B’ stands for bursa and not bone marrow as commonly believed.

BCRs

B cells, unlike the other two classes of lymphocytes, T cells and natural killer cells, express B cell receptors (BCRs) on their cell membrane. BCRs allow the B cell to bind to a foreign antigen, against which it will initiate an antibody response.

Development

B cells develop from hematopoietic stem cells (HSCs) that originate from bone marrow. HSCs first differentiate into multipotent progenitor (MPP) cells, then common lymphoid progenitor (CLP) cells. From here, their development into B cells occurs in several stages (shown in image to the right), each marked by various gene expression patterns and immunoglobulin H chain and L chain gene loci arrangements, the latter due to B cells undergoing V(D)J recombination as they develop.

B cells undergo two types of selection while developing in the bone marrow to ensure proper development, both involving B cell receptors (BCR) on the surface of the cell. Positive selection occurs through antigen-independent signaling involving both the pre-BCR and the BCR. If these receptors do not bind to their ligand, B cells do not receive the proper signals and cease to develop.

Negative selection occurs through the binding of self-antigen with the BCR; If the BCR can bind strongly to self-antigen, then the B cell undergoes one of four fates: clonal deletion, receptor editing, anergy, or ignorance (B cell ignores signal and continues development). This negative selection process leads to a state of central tolerance, in which the mature B cells do not bind self antigens present in the bone marrow.

T1 and T2

To complete development, immature B cells migrate from the bone marrow into the spleen as transitional B cells, passing through two transitional stages: T1 and T2. Throughout their migration to the spleen and after spleen entry, they are considered T1 B cells. Within the spleen, T1 B cells transition to T2 B cells. T2 B cells differentiate into either follicular (FO) B cells or marginal zone (MZ) B cells depending on signals received through the BCR and other receptors. Once differentiated, they are now considered mature B cells, or naive B cells.

The Immune System

The Immune system is a complex network of cells (such as lymphocytes) and organs that work together to defend the body against foreign substances (antigens) such as bacteria, a virus or tumor cell.  When the body discovers such a substance several kinds of cells go into action in what is called an immune response.  Below is a description of some of the cells that are part of the immune system.

Lymphocyte

Lymphocytes are cells that circulate in your blood that are part of the immune system. There are two main types lymphocytes: T cells and B cells. B cells produce antibody molecules that can latch on and destroy invading viruses or bacteria. T cells are direct fighters of foreign invaders and also produced cytokines, which are biological substances that help activate other parts of the immune system. One such part is called macrophages. These macrophages act to clean up the invaders and the dead tissue after an immune response.

Macrophages

Macrophages are the body’s first line of defense and have many roles.  A macrophage is the first cell to recognize and engulf foreign substances (antigens).  Macrophages break down these substances and present the smaller proteins to the T lymphocytes.  (T cells are programmed to recognize, respond to and remember antigens).  Macrophages also produce substances called cytokines that help to regulate the activity of lymphocytes.

Dendritic Cells

They are known as the most efficient antigen-presenting cell type with the ability to interact with T cells and initiate an immune response.  Dendritic cells are receiving increasing scientific and clinical interest due to their key role in the immune response and potential use with tumor vaccines.

White Blood Cells

There are different types of white blood cells that are part of the immune response.  Neutrophils or granulocytes are the most common immune cells in the body.  With an infection, their number increases rapidly.  They are the major components of pus and are found around most common inflammations.  Their job is to eat and destroy foreign material.  Basophils and eosinophils are white blood cells that contain large granules inside the cell.  They interact with certain foreign materials.  Their increased activity may lead to an allergic reaction.

The immune response is a coordinated effort.  All of the immune cells work together, so they need to communicate with each other.  They do this by secreting increased levels of a special protein molecule called cytokines that act on other cells.  There are many different cytokines.  Examples of these are interleukins, interferons, tumor necrosis factors, and colony-stimulating factors.  Some immunotherapy treatment strategies involve giving larger amounts of these proteins by an injection or infusion.  This is done in the hope of stimulating the cells of the immune system to act more effectively or to make the tumor cells more recognizable to the immune system.

Caution:

There are people who promote unproven therapies as immune system boosters.  Be careful when evaluating these claims.  The following are types of immunotherapies that are commonly and legitimately used in traditional and scientific medical practice.

How antibodies work

When an alien substance enters the body, the immune system is able to recognize it as foreign because molecules on the surface of the antigen differ from those found in the body. To eliminate the invader, the immune system calls on a number of mechanisms, including one of the most important—antibody production. Antibodies are produced by specialized white blood cells called B lymphocytes (or B cells). When an antigen binds to the B-cell surface, it stimulates the B cell to divide and mature into a group of identical cells called a clone. The mature B cells, called plasma cells, secrete millions of antibodies into the bloodstream and lymphatic system.

As antibodies circulate, they attack and neutralize antigens that are identical to the one that triggered the immune response. Antibodies attack antigens by binding to them. The binding of an antibody to a toxin, for example, can neutralize the poison simply by changing its chemical composition; such antibodies are called antitoxins. By attaching themselves to some invading microbes, other antibodies can render such microorganisms immobile or prevent them from penetrating body cells.

Bursting

In other cases the antibody-coated antigen is subject to a chemical chain reaction with complement, which is a series of proteins found in the blood. The complement reaction either can trigger the lysis (bursting) of the invading microbe or can attract microbe-killing scavenger cells that ingest, or phagocytose, the invader. Once begun, antibody production continues for several days until all antigen molecules are removed. Antibodies remain in circulation for several months, providing extended immunity against that particular antigen.

Antibodies and B cells

B cells and antibodies together provide one of the most important functions of immunity, which is to recognize an invading antigen and to produce a tremendous number of protective proteins that scour the body to remove all traces of that antigen. Collectively B cells recognize an almost limitless number of antigens; however, individually each B cell can bind to only one type of antigen. B cells distinguish antigens through proteins, called antigen receptors, found on their surfaces. An antigen receptor is basically an antibody protein that is not secreted but is anchored to the B-cell membrane.

All antigen receptors found on a particular B cell are identical, but receptors located on other B cells differ. Although their general structure is similar, the variation lies in the area that interacts with the antigen—the antigen-binding, or antibody-combining, site. This structural variation among antigen-binding sites allows different B cells to recognize different antigens. The antigen receptor does not actually recognize the entire antigen; instead it binds to only a portion of the antigen’s surface, an area called the antigenic determinant or epitope. Binding between the receptor and epitope occurs only if their structures are complementary. If they are, epitope and receptor fit together like two pieces of a puzzle, an event that is necessary to activate B-cell production of antibodies.

Antibody structure and classes

Each antibody molecule is essentially identical to the antigen receptor of the B cell that produced it. The basic structure of these proteins consists of two pairs of polypeptide chains (lengths of amino acids linked by peptide bonds) that form a flexible Y shape. The stem of the Y consists of one end of each of two identical heavy chains, while each arm is composed of the remaining portion of a heavy chain plus a smaller protein called the light chain.

The two light chains also are identical. Within particular classes of antibodies the stem and the bottom of the arms are fairly similar and thus are called the constant region. The tips of the arms, however, are highly variable in sequence. It is these tips that bind antigen. Thus each antibody has two identical antigen-binding sites, one at the end of each arm, and the antigen-binding sites vary greatly among antibodies.

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