{"id":6743,"date":"2026-06-09T15:22:08","date_gmt":"2026-06-09T19:22:08","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/?post_type=chapter&p=6743"},"modified":"2026-06-09T15:25:14","modified_gmt":"2026-06-09T19:25:14","slug":"t-and-b-lymphocyte-development-and-selection","status":"web-only","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/chapter\/t-and-b-lymphocyte-development-and-selection\/","title":{"raw":"Section 7:\u00a0 T and B Lymphocyte Development and Selection","rendered":"Section 7:\u00a0 T and B Lymphocyte Development and Selection"},"content":{"raw":"

T Cell Development and Selection<\/strong><\/span><\/h3>\r\n

T cells<\/strong>, arise from bone marrow hematopoietic cells and migrate to the thymus<\/strong> to mature through three stages.<\/p>\r\n

1.\u00a0 TCR Production:\u00a0 <\/strong>In the thymic cortex, T cells undergo somatic recombination to express a unique<\/strong> and functional\u00a0T Cell Receptor (TCR)<\/strong> and are then nurtured; those without a functional TCR undergo apoptosis<\/strong> ('death by neglect'<\/strong>).<\/p>\r\n

2.\u00a0 Positive Selection:<\/strong>\u00a0 In the next step of maturation, termed positive selection<\/strong>, the T cells encounter cortical thymocytes that display Major Histocompatibility Complex (MHC)<\/strong> molecules (self identity transmembrane protein complexes).\u00a0 T cells that bind weakly or moderately<\/strong> to these MHC are chosen for further maturation, while those that do not bind or bind too strongly are eliminated.\u00a0 At this point in time, the surviving T cells commit to expressing either CD8<\/strong> or CD4<\/strong> receptors before entering the thymic medulla<\/strong>, where negative selection<\/strong> occurs.<\/p>\r\n

3.\u00a0 Negative Selection:\u00a0<\/strong> T cells are exposed to medullary thymic cells and APCs that are displaying a large array of self-peptides on their MHC molecules<\/strong>.\u00a0 T cells that bind too strongly are induced to undergo apoptosis to prevent autoimmunity.<\/p>\r\n\r\n

\r\n

Positive and Negative Selection:\u00a0 Preventing Autoimmunity\u00a0<\/strong><\/p>\r\n\r\n<\/header>\r\n

\r\n\r\nDuring Positive Selection in the Thymic Cortex:<\/strong>\r\n\r\n\r\n\r\n\r\n
CD4+<\/sup> T cells<\/strong><\/span><\/td>\r\nThose that bind<\/strong> to thymic self-peptides <\/strong>displayed on MHC Class II<\/strong>\u00a0molecules (MHC-II) <\/strong>are nurtured and develop CD4+<\/sup> receptors \u2192 Positive Selection.\r\n\r\nThose that either do not bind<\/strong> or bind too strongly<\/strong> to thymic self-peptide-MHC-II complexes undergo apoptosis<\/strong> ('death by neglect', preventing autoimmunity).<\/td>\r\n<\/tr>\r\n
CD8+<\/sup> T cells<\/strong><\/span><\/td>\r\nThose that bind <\/strong>to thymic self-peptides <\/strong>displayed on MHC Class I (MHC-I)<\/strong> are nurtured and develop CD8+<\/sup> receptors \u2192 Positive Selection.\r\n\r\nThose that either do not bind<\/strong> or bind too strongly<\/strong> to self MHC-I undergo apoptosis<\/strong>\u00a0('death by neglect', preventing autoimmunity).<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\nDuring Negative Selection in the Thymic Medulla:<\/strong>\r\n\r\n\r\n\r\n\r\n
CD4+<\/sup> T cells<\/strong><\/span><\/td>\r\nThose that weakly<\/strong> bind self-peptides<\/strong> displayed on MHC-II of APCs mature into CD4+<\/sup> Effectors<\/strong> (Helper T cells<\/strong>).\r\n\r\nThose binding\u00a0moderately<\/strong> become CD4+<\/sup><\/strong> Regulatory T (Treg<\/sub>) cells<\/strong>\u00a0that suppress effector T cell proliferation.\r\n\r\nThose that strongly<\/strong> bind self-peptides<\/strong> displayed on MHC-II of APCs undergo apoptosis<\/strong> ('death by neglect', preventing autoimmunity).<\/td>\r\n<\/tr>\r\n
CD8+<\/sup> T cells<\/strong><\/span><\/td>\r\nThose that weakly<\/strong> bind self-antigens<\/strong> displayed on MHC-I of APCs mature into CD8+<\/sup> Effectors<\/strong> (Cytotoxic T cells<\/strong>).\r\n\r\nThose binding moderately<\/strong> become CD8+<\/sup> Regulatory T cells<\/strong>.\r\n\r\nThose that strongly<\/strong> bind self-antigens<\/strong> displayed on MHC-I of APCs undergo apoptosis<\/strong>\u00a0('death by neglect', preventing autoimmunity).<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n*Note: MHC (Major Histocompatibility Complex) proteins were previously known as HLA (Human Leukocyte Antigens).\r\n\r\nMHC Class I<\/strong> are found on almost all nucleated cells in your body, and present normal antigens from self-proteins and will also present abnormal\/foreign antigens when the cell is compromised.\r\n\r\nMHC Class II<\/strong> are expressed only by APCs which include macrophages, dendritic cells, and B cells and are used to present phagocytosed foreign antigens to activate immune cells.\r\n\r\n<\/div>\r\n<\/div>\r\nAfter negative selection, the T cells are now self-restricted and self-tolerant na\u00efve T cells<\/strong> that can safely leave the thymus and enter the bloodstream<\/strong> and continuously recirculate through secondary lymphoid organs<\/strong> (like the spleen, lymph nodes, and tonsils) to patrol for foreign antigens.\u00a0 T cells are self-restricted meaning they bind foreign antigens only when presented on MHCs.\u00a0 T cells are self-tolerant meaning that T cells will not be activated by self-antigens.\r\n\r\n[caption id=\"attachment_6706\" align=\"alignnone\" width=\"179\"]\"Lymphoid<\/a> Lymphoid progenitors (immature T cells) migrate from the bone marrow to the thymic cortex. Here they develop through a number of intermediate stages termed double-negative (DN) 1 to 4 where the cells remain negative for both the CD4 and CD8 co-receptors. Between DN1-4, the immature T cells that express unique and functional TCR are nurtured, while those that do not undergo apoptosis ('death by neglect'). T cells then express both CD4 and CD8 receptors becoming double positive (DP) and go through a process called Positive Selection. In positive selection DP T cells are exposed to cortical thymic epithelial cells (cTEC) that are displaying self-antigens on MHC-I and MHC-II. DP T cells that preferentially bind to the MHC-I complex will then repress CD4 expression and express only CD8 receptors, becoming CD8+ SP (single positive) cells. Likewise, DP T cells that preferentially bind to the MHC-II complex will then repress CD8 expression and express only CD4 receptors, becoming CD4+ SP (single positive) cells. These CD4+ and CD8+ cells migrate into the medulla of the thymus where they undergo negative selection. In this process, both medullary TEC (mTEC) and APCs display a large array of self peptides on their MHC molecules. T cells that bind strongly to the self-antigen will undergo apoptosis. T cells that bind weakly will become Effector Cells (either CD8+ Cytotoxic T cells or CD4+ Helper T cells). T cell that bind moderately will become Regulatory T cells.[\/caption]\r\n

B Cell Development and Selection<\/strong><\/span><\/h3>\r\n

B cell development is similar to T cell development, in that B cells arise in the bone marrow<\/strong> from hemopoietic stem cells and through somatic recombination each develop a unique B cell receptor (BCR)<\/strong>.\u00a0 The B cells then undergo both positive and negative selection, ensuring that: (1) BCRs are functional and that (2) B cells do not bind to self-antigens.\u00a0 B cells that either lack a functioning BCR or bind to self-antigens are induced to undergo apoptosis.\u00a0 The surviving B cells travel to the spleen, mature into self-tolerant na\u00efve B cells<\/strong> that then migrate to and populate lymphatic tissues.<\/p>\r\n ","rendered":"

T Cell Development and Selection<\/strong><\/span><\/h3>\n

T cells<\/strong>, arise from bone marrow hematopoietic cells and migrate to the thymus<\/strong> to mature through three stages.<\/p>\n

1.\u00a0 TCR Production:\u00a0 <\/strong>In the thymic cortex, T cells undergo somatic recombination to express a unique<\/strong> and functional\u00a0T Cell Receptor (TCR)<\/strong> and are then nurtured; those without a functional TCR undergo apoptosis<\/strong> (‘death by neglect’<\/strong>).<\/p>\n

2.\u00a0 Positive Selection:<\/strong>\u00a0 In the next step of maturation, termed positive selection<\/strong>, the T cells encounter cortical thymocytes that display Major Histocompatibility Complex (MHC)<\/strong> molecules (self identity transmembrane protein complexes).\u00a0 T cells that bind weakly or moderately<\/strong> to these MHC are chosen for further maturation, while those that do not bind or bind too strongly are eliminated.\u00a0 At this point in time, the surviving T cells commit to expressing either CD8<\/strong> or CD4<\/strong> receptors before entering the thymic medulla<\/strong>, where negative selection<\/strong> occurs.<\/p>\n

3.\u00a0 Negative Selection:\u00a0<\/strong> T cells are exposed to medullary thymic cells and APCs that are displaying a large array of self-peptides on their MHC molecules<\/strong>.\u00a0 T cells that bind too strongly are induced to undergo apoptosis to prevent autoimmunity.<\/p>\n

\n
\n

Positive and Negative Selection:\u00a0 Preventing Autoimmunity\u00a0<\/strong><\/p>\n<\/header>\n

\n

During Positive Selection in the Thymic Cortex:<\/strong><\/p>\n\n\n\n\n
CD4+<\/sup> T cells<\/strong><\/span><\/td>\nThose that bind<\/strong> to thymic self-peptides <\/strong>displayed on MHC Class II<\/strong>\u00a0molecules (MHC-II) <\/strong>are nurtured and develop CD4+<\/sup> receptors \u2192 Positive Selection.<\/p>\n

Those that either do not bind<\/strong> or bind too strongly<\/strong> to thymic self-peptide-MHC-II complexes undergo apoptosis<\/strong> (‘death by neglect’, preventing autoimmunity).<\/td>\n<\/tr>\n

CD8+<\/sup> T cells<\/strong><\/span><\/td>\nThose that bind <\/strong>to thymic self-peptides <\/strong>displayed on MHC Class I (MHC-I)<\/strong> are nurtured and develop CD8+<\/sup> receptors \u2192 Positive Selection.<\/p>\n

Those that either do not bind<\/strong> or bind too strongly<\/strong> to self MHC-I undergo apoptosis<\/strong>\u00a0(‘death by neglect’, preventing autoimmunity).<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

During Negative Selection in the Thymic Medulla:<\/strong><\/p>\n\n\n\n\n
CD4+<\/sup> T cells<\/strong><\/span><\/td>\nThose that weakly<\/strong> bind self-peptides<\/strong> displayed on MHC-II of APCs mature into CD4+<\/sup> Effectors<\/strong> (Helper T cells<\/strong>).<\/p>\n

Those binding\u00a0moderately<\/strong> become CD4+<\/sup><\/strong> Regulatory T (Treg<\/sub>) cells<\/strong>\u00a0that suppress effector T cell proliferation.<\/p>\n

Those that strongly<\/strong> bind self-peptides<\/strong> displayed on MHC-II of APCs undergo apoptosis<\/strong> (‘death by neglect’, preventing autoimmunity).<\/td>\n<\/tr>\n

CD8+<\/sup> T cells<\/strong><\/span><\/td>\nThose that weakly<\/strong> bind self-antigens<\/strong> displayed on MHC-I of APCs mature into CD8+<\/sup> Effectors<\/strong> (Cytotoxic T cells<\/strong>).<\/p>\n

Those binding moderately<\/strong> become CD8+<\/sup> Regulatory T cells<\/strong>.<\/p>\n

Those that strongly<\/strong> bind self-antigens<\/strong> displayed on MHC-I of APCs undergo apoptosis<\/strong>\u00a0(‘death by neglect’, preventing autoimmunity).<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

*Note: MHC (Major Histocompatibility Complex) proteins were previously known as HLA (Human Leukocyte Antigens).<\/p>\n

MHC Class I<\/strong> are found on almost all nucleated cells in your body, and present normal antigens from self-proteins and will also present abnormal\/foreign antigens when the cell is compromised.<\/p>\n

MHC Class II<\/strong> are expressed only by APCs which include macrophages, dendritic cells, and B cells and are used to present phagocytosed foreign antigens to activate immune cells.<\/p>\n<\/div>\n<\/div>\n

After negative selection, the T cells are now self-restricted and self-tolerant na\u00efve T cells<\/strong> that can safely leave the thymus and enter the bloodstream<\/strong> and continuously recirculate through secondary lymphoid organs<\/strong> (like the spleen, lymph nodes, and tonsils) to patrol for foreign antigens.\u00a0 T cells are self-restricted meaning they bind foreign antigens only when presented on MHCs.\u00a0 T cells are self-tolerant meaning that T cells will not be activated by self-antigens.<\/p>\n

\"Lymphoid<\/a>
Lymphoid progenitors (immature T cells) migrate from the bone marrow to the thymic cortex. Here they develop through a number of intermediate stages termed double-negative (DN) 1 to 4 where the cells remain negative for both the CD4 and CD8 co-receptors. Between DN1-4, the immature T cells that express unique and functional TCR are nurtured, while those that do not undergo apoptosis (‘death by neglect’). T cells then express both CD4 and CD8 receptors becoming double positive (DP) and go through a process called Positive Selection. In positive selection DP T cells are exposed to cortical thymic epithelial cells (cTEC) that are displaying self-antigens on MHC-I and MHC-II. DP T cells that preferentially bind to the MHC-I complex will then repress CD4 expression and express only CD8 receptors, becoming CD8+ SP (single positive) cells. Likewise, DP T cells that preferentially bind to the MHC-II complex will then repress CD8 expression and express only CD4 receptors, becoming CD4+ SP (single positive) cells. These CD4+ and CD8+ cells migrate into the medulla of the thymus where they undergo negative selection. In this process, both medullary TEC (mTEC) and APCs display a large array of self peptides on their MHC molecules. T cells that bind strongly to the self-antigen will undergo apoptosis. T cells that bind weakly will become Effector Cells (either CD8+ Cytotoxic T cells or CD4+ Helper T cells). T cell that bind moderately will become Regulatory T cells.<\/figcaption><\/figure>\n

B Cell Development and Selection<\/strong><\/span><\/h3>\n

B cell development is similar to T cell development, in that B cells arise in the bone marrow<\/strong> from hemopoietic stem cells and through somatic recombination each develop a unique B cell receptor (BCR)<\/strong>.\u00a0 The B cells then undergo both positive and negative selection, ensuring that: (1) BCRs are functional and that (2) B cells do not bind to self-antigens.\u00a0 B cells that either lack a functioning BCR or bind to self-antigens are induced to undergo apoptosis.\u00a0 The surviving B cells travel to the spleen, mature into self-tolerant na\u00efve B cells<\/strong> that then migrate to and populate lymphatic tissues.<\/p>\n

 <\/p>\n

Media Attributions<\/h2>