Figure 1.
Figure 1. Events in B-cell development. / The development and maturation process of B cells begins in the bone marrow. Here, the “pre-B cell” arises from the “progenitor (Pro) B cell” following rearrangement of the immunoglobulin heavy chain gene (symbolized with horizontal lines in black). Subsequently, rearrangement of the light chain genes occurs resulting in the expression of the whole immunoglobulin molecule on the cell surface, serving as an antigen receptor. With the production of this “immature” B cell, the initial phase of B-cell development is, thereby, completed. The “immature” B cell is so defined since it is unable to initiate an immune response following the presentation of a foreign antigen. The B-cell attains this ability only on leaving the bone marrow, passing through the blood stream and entering the peripheral lymphoid tissue. Here, the B cell migrates to the outer region of the lymph node in the “primary” follicles and, later, to the follicle mantles. This differentiation step is associated with the additional expression of IgD. These IgM+/IgD+ B cells are known as “naive mature B-cells”. When these cells come into contact with antigen (AG), which can bind to their immunoglobulin molecules, they transform into proliferating extrafollicular B blasts, from which short-lived plasma cells and “antigen-induced” or “primed” B cells are derived. These “primed” B cells initiate and maintain the germinal center reaction, during which they transform into rapidly proliferating centroblasts. During the mitotic proliferation and differentiation of the centroblasts into centrocytes, somatic mutations in the variable region of the immunoglobulin genes are inserted in a randomized manner (the mutations are represented by vertical lines). The centrocytes with advantageous mutations (i.e. those which lead to an increase in the affinity of the immunoglobulin receptor) differentiate further, passing out of the germinal centre into long-lived plasma cells or into “memory” B cells. The latter remain in the marginal zone. FDC, folicular dendritic cell; , apoptosis. / As a result of the differentiation phases of B-cells and of the somatic mutation process, 3 major different mature forms of B-cells can be identified:. / • Naive mature B-cells (recirculating and sessile subtypes). / • Germinal center B-cells (centroblasts and centrocytes). / • Post germinal center B-cells which include memory B cells and long-lived plasma cells. / From all of these different B-cell forms, malignant B-cell lymphomas arise, which distinguish themselves clinically and which are characterized in their biological behavior not only by the transformation event but also by the inherent characteristics of the cell of origin. Classical Hodgkin lymphomas, in which the phenotypical and clinical features are predominantly determined by the transformation event, are an exception to this rule.

Events in B-cell development.

The development and maturation process of B cells begins in the bone marrow. Here, the “pre-B cell” arises from the “progenitor (Pro) B cell” following rearrangement of the immunoglobulin heavy chain gene (symbolized with horizontal lines in black). Subsequently, rearrangement of the light chain genes occurs resulting in the expression of the whole immunoglobulin molecule on the cell surface, serving as an antigen receptor. With the production of this “immature” B cell, the initial phase of B-cell development is, thereby, completed. The “immature” B cell is so defined since it is unable to initiate an immune response following the presentation of a foreign antigen. The B-cell attains this ability only on leaving the bone marrow, passing through the blood stream and entering the peripheral lymphoid tissue. Here, the B cell migrates to the outer region of the lymph node in the “primary” follicles and, later, to the follicle mantles. This differentiation step is associated with the additional expression of IgD. These IgM+/IgD+ B cells are known as “naive mature B-cells”. When these cells come into contact with antigen (AG), which can bind to their immunoglobulin molecules, they transform into proliferating extrafollicular B blasts, from which short-lived plasma cells and “antigen-induced” or “primed” B cells are derived. These “primed” B cells initiate and maintain the germinal center reaction, during which they transform into rapidly proliferating centroblasts. During the mitotic proliferation and differentiation of the centroblasts into centrocytes, somatic mutations in the variable region of the immunoglobulin genes are inserted in a randomized manner (the mutations are represented by vertical lines). The centrocytes with advantageous mutations (i.e. those which lead to an increase in the affinity of the immunoglobulin receptor) differentiate further, passing out of the germinal centre into long-lived plasma cells or into “memory” B cells. The latter remain in the marginal zone. FDC, folicular dendritic cell; , apoptosis

As a result of the differentiation phases of B-cells and of the somatic mutation process, 3 major different mature forms of B-cells can be identified:

• Naive mature B-cells (recirculating and sessile subtypes)

• Germinal center B-cells (centroblasts and centrocytes)

• Post germinal center B-cells which include memory B cells and long-lived plasma cells

From all of these different B-cell forms, malignant B-cell lymphomas arise, which distinguish themselves clinically and which are characterized in their biological behavior not only by the transformation event but also by the inherent characteristics of the cell of origin. Classical Hodgkin lymphomas, in which the phenotypical and clinical features are predominantly determined by the transformation event, are an exception to this rule.

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