A3 Antibody diversity and B lymphocyte-mediated immunity

Abstract

Towards the end of the 19th century, Koch and Ehrlich discovered that the serum of immunized animals contained substances (antitoxins) with the ability to neutralize the toxins of diphtheria and tetanus. At Christmas 1891 a group of children received diphtheria antitoxin, which cured them from this otherwise fatal disease. These experiments demonstrated that immunization can induce the formation of humoral substances, which have the ability to protect against infectious diseases. Half a century later, in 1952, Bruton described a patient with severe and recurrent respiratory tract infections and an AGAMMAGLOBULINEMIA. This milestone demonstrated the significant role of IMMUNOGLOBULINS in the defense against infections. Later on, through the pioneering work of Max Cooper and others, it was shown that B LYMPHOCYTES are the cells that produce ANTIBODIES, and that patients such as the one described above (X-linked AGAMMAGLOBULINEMIA or XLA) fail to produce ANTIBODIES because they lack B LYMPHOCYTES; B lymphocyte development in the BONE MARROW stops at the pre-B cell stage. Forty years after the initial discovery, the molecular basis for this disease was found: XLA is caused by structural defects in the gene encoding an enzyme that has been termed Bruton’s tyrosine kinase (Btk).