B-lymphocyte migration is also critical for effective adaptive immunity, although the patterns of migration differ from those of T cells. The initiation of B-cell responses to infection begins in secondary lymphoid organs and often depends on help from T cells. Therefore, this first stage of a B-cell response requires similar migratory activities of naive B cells as we described for naive T cells. However, secreted antibodies, mainly produced by B cell–derived plasma cells, perform the effector functions of B cells at sites distant from the plasma cells, and these antibodies, but not the plasma cells themselves, need to be delivered by the blood to infected tissues. During an acute microbial infection, plasma cells that have differentiated in the spleen, lymph nodes or mucosal lymphoid tissues are the main source of circulating antibodies specific for the microbe and, afterwards, long-lived plasma cells in the bone marrow continue to secrete antibodies for many years.

Recirculation of Naive Follicular B Cells

Naive follicular B cells use the same basic mechanisms as do naive T cells to home to and exit out of secondary lymphoid organs. There are different subsets of B cells, but the major subset responsible for most antibody production is called follicular B cells, and we will describe their migratory activities. Immature follicular B cells leave the bone marrow through the blood, enter the spleen through the marginal zone, and migrate to the periphery of the white pulp. As they mature further, the B cells express the chemokine receptor CXCR5, which promotes their movement into the white pulp in response to a chemokine called CXCL13, which is produced by follicular dendritic cells (FDCs) in lymphoid follicles. After the maturation is completed within the white pulp, naive follicular B cells reenter the circulation by an S1P-driven process and then recirculate to lymph nodes, mucosal lymphoid tissues, or back to the spleen. Homing of naive B cells from the blood into lymph nodes and Peyer patches in the intestine involves rolling inter actions on HEVs, chemokine activation of integrins, and stable arrest, as described earlier for naive T cells (Fig. 1). This process depends on the chemokine receptors CCR7, CXCR4, and CXCR5 on naive B cells and their respective ligands CCL19/ CCL21, CXCL12, and CXCL13. CCL19/CCL21 and CXCL12 are displayed by HEVs in lymph nodes and mediate the entry of naive and memory B cells initially into the outer T cell zone of the lymph nodes around the HEV. CXCL13 then draws B cells into the follicles (the B cell zone). There are no HEVs in the white pulp of the spleen and the mechanisms of homing of naive B cells into splenic white pulp are not well understood. Homing of naive B cells into Peyer patches in the small bowel wall involves CXCR5 and the integrin α4 β7 , which binds to MAdCAM-1. During the course of B-cell responses to protein antigens, B cells and helper T cells must directly interact and this is made possible by highly regulated movements of both cell types within the secondary lymphoid organs. These local migratory events and the chemokines that orchestrate them will be discussed in detail in Chapter 12. If a naive B cell is not activated by an antigen in a lymph node or the spleen after several hours, it will respond to the S1P gradient, exit into the circulation, and recirculate back into other secondary lymphoid organs. B cells in the lymph node will exit through efferent lymphatics and by the thoracic duct into the blood, and B cells in the spleen migrate to the marginal zone and then are carried by fluid through the red pulp into the circulation.

Fig1. Migration of B cells. Naive B cells enter lymph nodes and mucosal-associated lymphoid tissues through high endothelial venules (HEVs), migrate into follicles, become activated, and differentiate into anti body-producing cells, some of which are plasmablasts that enter the circulation and migrate into bone marrow or mucosal tissues, where they fully differentiate into plasma cells. Immunoglobulin G (IgG)-secreting plasma cells may be generated in any lymphoid tissues. IgA-secreting plasma cells are produced mainly in mesenteric lymph nodes or mucosa-associated lymphoid tissues and home back to mucosal tissues. Other B cells that enter follicles differentiate into memory B cells, some of which enter the circulation. The chemokine receptors and chemokines involved in these steps are shown. Adhesion molecules are also involved in migration out of the HEVs and blood vessels in tissues, as described in the text.

Migration of Antibody-Secreting Plasmablasts and Memory B Cells

 Plasmablasts derived from follicular B cells exit out of second ary lymphoid organs and home to bone marrow or mucosal tissues, where they differentiate into long-lived plasma cells (see Fig. 1). If a naive B cell is activated by an antigen in a sec ondary lymph node, it will differentiate into antibody-secreting cells called plasmablasts. Some of these plasmablasts reside outside of follicles in the secondary lymphoid organ and differenti ate into plasma cells with short life spans that secrete antibodies locally. However, as a response to a protein antigen progresses, and T cells help B cells, plasmablasts are also generated in the germinal centers of follicles. These plasmablasts exit the secondary lymphoid tissues by an S1P dependent mechanism and enter the blood. Many of these cells home to the bone marrow and some to mucosal tissues, where they mature into long-lived plasma cells that stay in these tis sues and secrete antibodies for long periods.

Most memory B cells are generated in germinal centers of secondary lymphoid organs along with plasmablasts. Some memory B cells migrate to bone marrow and mucosal sites with the plasmablasts, whereas other memory B cells appear to recirculate through secondary lymphoid organs. Reactivation of memory B cells on reexposure to microbial protein antigens induces new germinal center reactions in the lymphoid organs. Overall, the mechanisms that govern memory B-cell migration and recirculation are not well understood.

Subsets of activated B cells committed to producing particular types of antibodies migrate from secondary lymphoid organs into specific tissues, where they differentiate into long lived plasma cells (see Fig. 1). As we will describe in later chapters, during their responses to an antigen, B cells may differentiate into cells that produce different types of antibodies, called classes (or isotypes), each of which performs a distinct set of effector functions. The genetic changes that determine which Ig class will be expressed by B cells occur before differentiation into plasmablasts and finally into plasma cells. B cells that are committed to secreting antibodies of the IgG class will differentiate into plasmablasts that mostly migrate to the bone marrow and, accordingly, most plasma cells residing in the bone marrow produce IgG antibodies, which are then distributed throughout the body via the bloodstream. B cells that are activated within MALTs usually become committed to expression of the IgA class of antibody and IgA-producing plasmablasts home specifically to mucosal tissues. The local differentiation within the mucosal lymphoid tissues of B cells into IgA-secreting cells, combined with the homing of these cells into the mucosa, optimizes IgA defense against microbial invasion through the mucosal barriers. As we will discuss in more detail in Chapter 14, IgA is efficiently secreted into the lumen of tissues lined by mucosal epithelia, such as the gut and respiratory tract.

The mechanisms by which different B-cell populations migrate to different tissues are similar to the mechanisms we described for tissue-specific migration of effector T cells and depend on expression of distinct combinations of adhesion molecules and chemokine receptors on each B-cell subset. For example, bone marrow–homing IgG-secreting plasma cells express VLA-4 and CXCR4, which bind respectively to VCAM-1 and CXCL12 expressed on bone marrow sinusoidal endothelial cells. In contrast, mucosa-homing IgA-secreting plasma cells express α4 β7 and CCR9, which bind respectively to MAdCAM-1 and CCL25 on mucosal endothelial cells. IgG secreting B cells are also recruited to chronic inflammatory sites in various tissues and this homing pattern can be attributed to VLA-4 and CXCR3 on these B cells binding to VCAM-1, CXCL9, and CXCL10, which are often found on the endothelial surface at sites of chronic inflammation.

اخر الاخبار

اخبار العتبة العباسية المقدسة

العتبة العباسية المقدسة تقيم مجلس عزاء لإحياء ذكرى شهادة الإمام جعفر الصادق (عليه السلام)

بعد مرور أربع سنوات على تأسيسه قسم شؤون المعارف يعلن منجزات مركز التراث الإسلامي في إيران

قسم الشؤون الفكرية يختتم مسابقة (معز المؤمنين الثقافية) ويكرِّم الفائزين في كربلاء وبابل

قسم الصيانة ينفذ أعمالًا تطويرية في مجمع الإمام الهادي (عليه السلام)

المزيد

الآخبار الصحية

الشاشات ليست مجرد ترفيه.. تأثيرات طويلة المدى على دماغ طفلك

الأسباب الرئيسية لنقص الطاقة في الجسم

الكاكاو وتأثيره على العين.. نتائج واعدة من تجارب مخبرية

طبيب يحذر: أطعمة شائعة الاستهلاك أخطر على صحتنا من التدخين

المزيد

الآخبار التكنلوجية

باحثون في "نيويورك أبوظبي" يطورون تقنيات لرصد وعلاج الأورام

جيتكس إفريقيا.. المغرب يجمع "رواد التكنولوجيا" من 103 دول

طاقم أرتميس 2 يحطم رقما قياسيا ويستعرض الجانب البعيد للقمر

"أرتيميس 2" تنطلق حول القمر وتحطم الرقم القياسي

المزيد

مواضيع ذات صلة

Rh Blood Types

O-A-B Blood Types

Allergy and Hypersensitivity

The Antiviral Response

Migration of Effector T Lymphocytes to Sites of Infection

Exit of Naive and Effector T Cells from Lymph Nodes

Lymphocytes are Responsible for Acquired Immunity

The Major Proinflammatory Cytokines of Innate Immunity

Migration of Naive T Cells Into Lymph Nodes

Migration of Neutrophils and Monocytes to Sites of Infection or Tissue Injury

Leukocyte-Endothelial Interactions and Leukocyte Recruitment into Tissues

Formation of Pus