University of Virginia Health System

Marginal Zone B Cell
(Monocytoid B cell, MALT B cell)

(a) Marginal zone lymphocyte- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

b. Marginal zone lymphocyte- Bone marrow aspirate smear, Wright-Giemsa stain, 1000x

Description

At least a subset of marginal zone (MZ) B cells has a characteristic morphology by light microscopy. On paraffin fixed sections of mucosal associated lymphoid tissue (MALT), the splenic marginal zone, lymph nodes (dome area of secondary lymph follicles in Peyer's patches, inside sinuses), and the subepithelial region of the tonsils, they have a "fried egg" appearance due to their abundant cytoplasm. Those seen occasionally on a normal peripheral blood smear (a) and in the peripheral blood of patients with splenic marginal zone B cell lymphomas (maltomas) also have a characteristic appearance. They are large lymphocytes with a low nuclear:cytoplasmic ratio. The nucleus usually is eccentric in location, and the nuclear chromatin is mature with less clumping than is seen in small lymphocytes. A nucleolus may be visible, especially in patients with maltomas (b). The cytoplasm is abundant, and the color ranges from grey to light blue in color. MZ B cells must be distinguished from large granular lymphocytes (LGLs), and prolymphocytes. LGLs are approximately the same size and shape, but have distinct azurophilic granules in the cytoplasm. Prolymphocytes are large lymphocytes, but can be distinguished from MZ B cells by having a much deeper blue (basophilic) cytoplasm, and the nuclear chromatin is more immature and clumped, and prominent nucleoli are usually visible.

Development, Function and Trafficking:

MZ B cells are so named because they develop in the marginal zone of the spleen. In congenital asplenic individuals and in those who have had splenectomy, MZ B cells do not develop. In the rodent, MZ B cells are found only in the spleen, but in humans they circulate and are found in several other sites: MALT areas, lymph nodes (dome area of secondary follicles, subcapsular sinuses), and in subepithelial areas of tonsils.

The marginal zones in the spleen are located between the white and red pulp, and in addition to MZ B cells contain macrophages, dendritic and stromal cells. Blood flowing through the spleen exits the circulation through follicular arterioles into the marginal zones, making these areas ideally situated for immune reactive cells present in these areas to come in contact with blood-borne pathogens and self antigens (e.g. surface antigens on red cells and platelets).

Circulating näive B and T cells enter the white pulp through marginal zones and home to follicles (B cells) or periarteriolar sheaths (T cells). Näive B cells are thought to enter follicles where they undergo antigenic stimulation. Depending on the strength of the B cell receptor (BCR) signaling the cells either remain in the follicles and undergo T cell-dependent proliferation and differentiation to form plasma cells and memory B cells, or leave the follicles and enter marginal zones where they undergo T cell-independent proliferation and differentiation to form plasma cells and memory B cells (positive selection). Strong signaling favors follicular development while weak signaling favors marginal zone development. In addition to the BCR signaling, many other factors are required for B cell development following antigenic stimulation, e.g. Bruton's tyrosine kinase (Btk) is crucial for T cell-dependent development, while Notch and NF-kappaB signaling are crucial for MZ B cell development.

Considering the cellular milieu of the marginal zones, näive B cells probably can be stimulated by antigen and undergo proliferation and differentiation without first entering follicles. Both pathways probably are operative in other marginal zone sites (e.g. MALT areas).

MZ B cells are predominantly memory B cells that express IgM (strong), IgD (low), CD27, along with pan B cell markers, e.g. CD19 and CD21 (strong). Some rather unique markers include CD1c (MHC-like) and CD148 (receptor tyrosine phosphatase). They are CD5, CD10, and CD23 negative. Most MZ B cells are long-lived with some surviving the lifespan of the host. Their longevity probably is due in part to constant weak signaling from self antigens and blood-borne pathogens.  

General References:

1. Pillai S, Cariappa A., Moran ST. Marginal zone B cells. Annu Rev Immunal 2005; 23:161-96

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