Lymphopoiesis

Lymphopoiesis is the developmental process by which lymphocytes are produced. The principal products are B cells, T cells, and natural killer (NK) cells, which participate in adaptive and innate immunity. In most adults, B cell development occurs in the bone marrow, T cell development in the thymus, and NK cells arise from lymphoid progenitors in bone marrow and peripheral tissues. The process begins with hematopoietic stem cells differentiating into common lymphoid progenitors.

B cell development, or B lymphopoiesis, proceeds in the bone marrow through stages known as pro-B, pre-B, and immature B cells, culminating in mature naive B cells with functional B cell receptors. Immunoglobulin gene rearrangements and quality control steps ensure self-tolerance before B cells migrate to peripheral lymphoid organs.

T cell development, or T lymphopoiesis, occurs in the thymus. Developing thymocytes progress from double-negative (CD4− CD8−), through the double-positive (CD4+ CD8+) stage, to single-positive lineages (CD4+ or CD8+). T cell receptor gene rearrangement and thymic selection—positive selection for MHC recognition and negative selection against self-reactivity—shape the mature T cell repertoire, which then enters the circulation.

NK cell development arises from lymphoid progenitors and leads to innate cytotoxic lymphocytes that lack antigen receptors but can recognize stressed or infected cells and tumors. NK cells populate blood and tissues and provide rapid responses alongside adaptive lymphocytes.

Regulation of lymphopoiesis depends on specialized microenvironments, including bone marrow and thymic niches, and cytokines such as interleukin-7. Age-related thymic involution reduces T cell output, and defects in lymphopoiesis can contribute to immunodeficiency or hematologic malignancies.

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