Differentiation of B Lymphocytes: Hybridomas and Monoclonal Antibodies

A dramatic example of the degree of specialization that can accompany cellular differentiation is pro­vided by a family of white blood cells called lympho­cytes.

There are two major types of lymphocytes T lymphocytes and B lymphocytes. Both originate from pluripotent stem cells in the hemopoietic tissues of the embryo (i.e., the liver and bone marrow).

From there the stem cells migrate to and colonize the pri­mary lymphoid tissues; these tissues include the thy­mus (found in both mammals and birds) and the bursa of Fabricius (found only in birds, there is no mamma­lian equivalent). The stem cells that colonize the thy­mus gland (i.e., prothymocytes) give rise there to the T lymphocytes (“T” = “thymus-derived”).

Many T lym­phocytes leave the thymus and seed secondary lym­phoid tissues such as lymph nodes, spleen, tonsils, and adenoids. Stem cells colonizing the bursa of Fabricius give rise to the B lymphocytes (“B” = “bursa- derived”). In mammals, which have no bursa, B lym­phocytes are derived from colonized secondary lym­phoid tissues and from the bone marrow itself. Both kinds of lymphocytes protect the body against infection by microorganisms, parasites, and other agents and are responsible for the body’s capacity to develop immunity against certain diseases. In the case of the B lymphocytes, immunity stems, from the production and secretion of antibodies or im­munoglobulins into the bloodstream by these cells.

The immunoglobulins secreted by the B lymphocytes combine with antigens in the surfaces of viruses, bac­teria, and other agents of infection, ultimately leading to the destruction of the antigen-bearing material. The body’s lymphoid tissues can give rise to more than a million different lines of B lymphocytes, each line developing an independent capacity for producing antibodies against a specific antigenic determinant.

The antibodies secreted by lymphocytes are the products of the transcription and translation of two types of genes called V and C genes. Despite the pres­ence of many hundreds of different V and C genes in each lymphocyte, only one pair of V and C genes is ex­pressed by each line of lymphocytes. The specific V and C genes expressed by an antibody-producing lym­phocyte are not only expressed to the exclusion of other V and C genes but also to the exclusion of most other structural genes in the cell.

Like the B lymphocytes, T lymphocytes also protect the body against infection. Whereas the immunity conferred by the B lymphocytes is humorally medi­ated (i.e., it stems from antibodies secreted into the blood plasma), T lymphocytes provide cell-mediated immunity, that is, T lymphocytes interact directly with bacteria, viruses, or parasitic cells.

Hybridomas and Monoclonal Antibodies:

Because of the highly specific nature of the antibodies pro­duced by differentiated B lymphocytes, cultures of the many lines of these cells have long been contem­plated as a source of antibodies for clinical applica­tion.

Whereas the highly differentiated B lympho­cytes cannot be cultured, hybrid cells formed by fusing malignant myeloma cells with B lymphocytes do proliferate in culture and synthesize their respec­tive antibodies. These hybridomas can be separately cloned to yield large cultures of cells producing spe­cific antibodies. Antibodies produced by this process are called monoclonal antibodies.