Molecular and cellular mechanisms underlying defective antibody responses.

Primary immune deficiency is caused by genetic mutations that result in immune dysfunction and subsequent susceptibility to infection. Over the last decade there has been a dramatic increase in the number of genetically defined causes of immune deficiency including those which affect B-cell function. This has not only identified critical nonredundant pathways that control the generation of protective antibody responses but also revealed that immunodeficiency and autoimmunity are often closely linked. Here we explore the molecular and cellular mechanisms of these rare monogenic conditions that disrupt antibody production, which also have implications for understanding the causes of more common polygenic immune dysfunction.