CD19, CD20

CD19


Coreceptor with CD21

Earliest B cell antigen in fetal tissue

Regulates B cell development, activation and differentiation (J Immunol 2003;171:5921)

May define intrinsic and antigen receptor-induced signaling thresholds critical for clonal expansion of the B cell pool and humoral immunity (Curr Dir Autoimmun 2005;8:55)

More common in plasma cells in steroid resistant ulcerative colitis than Crohn’s disease (Virchows Arch 2006;448:412); presence of CD19+ cells in intestinal mucosa may predict long remission after infliximab (anti-TNF alpha) therapy in Crohn’s disease (Hepatogastroenterology 2005;52:1128)

Uses: diagnosis of B cells and B cell disorders; may be more sensitive than CD20 to detect B cell acute leukemias (Zhongguo Shi Yan Xue Ye Xue Za Zhi 2005;13:943), to differentiate follicular lymphoma (dimmer CD19 in CD10+ B cells by flow cytometry) from reactive hyperplasia (AJCP 2005;124:576)

Flow cytometry images: follicular lymphoma with IgG light chain restriction; biphenotypic acute leukemia with CD19 and myeloperoxidase coexpression (figure B); hairy cell leukemia variant: A-CD20 (bright) and CD22+; B-CD11c+ and CD22+; C-CD103+ and CD25 negative; D-CD19+ and FMC7+; E-kappa+; F-lambda negative

Positive staining (normal): Pre B cells, B cells (considered a pan B cell antigen); first B cell antigen after HLA-DR, follicular dendritic cells

Positive staining (disease): B cell lymphomas and leukemias but often weak/negative in follicular lymphoma or diffuse large B cell lymphoma (Histopathology 2006;48:239, Cytometry B Clin Cytom 2005;63:28), occasional myeloid leukemias (AML-AJCP 1998;109:211; AML-M0-AJCP 2001;115:876; CML blast phase-AJCP 2004;121:836), occasional anaplastic large cell lymphoma by flow cytometry (AJCP 2003;119:205)

Negative staining: plasma cells, myeloma (AJCP 2004;121:482), most T cell lymphomas, often L&H cells in lymphocyte predominant Hodgkin’s lymphoma, often post-transplant B cell lymphoproliferative disorder

References: OMIM 107265



CD20


Also called L26, membrane spanning 4 domains (MS4A1)

33kd phosphoprotein with 3 hydrophobic regions that traverse the cell membrane, creating a structure similar to an ion channel that allows for the influx of calcium required for cell activation

Initially expressed on B cells after CD19/CD10 expression and before CD21/CD22 and surface immunoglobulin expression; retained on mature B cells until plasma cell development

Delivers early signal in B cell activation, allowing resting B cells to respond to later antigens

Closely related to FMC7, which recognizes a CD20 epitope (Leukemia 2003;17:1384), particularly if there is strong CD20 expression (AJCP 2003;120:754)

Rituximab is a chimeric murine-human anti-CD20 antibody used to treat B cell lymphomas; treatment may cause selection of CD20 negative (but CD79a+) tumor subclones (AJSP 2005;29:1399)

Rituximab is also used to treat autoimmune disorders (Clin Immunol 2005;117:207), TTP/HUS (Acta Cytol 2005;19:423), ABO incompatible transplantation (Transplant Proc 2005;37:1205) and transplant rejection (Clin Transplant 2005;19:137)

Anti CD20-antibody attached to radioisotopes is also used to treat B cell lymphomas (Clin Exp Med 2006;6:1)

Case reports: CD20+ T cell lymphomas (Am J Hematol 2002;71:331, AJCP 1994;102:483, Mod Path 2001;14:105, Mod Path 2000;13:1244); rarely stains nucleoli of malignant T cells (Acta Cytol 2005;49:365), but see J Clin Pathol 2004;57:442

Uses: commonly used marker for B cells

Micro images: normal lymph node #1; #2

angioimmunoblastic T cell lymphoma (figure d)

diffuse large B cell lymphoma - bone; brain-#1; #4 (figure A); #5 (intravascular); #6 (intravascular); liver; nasal cavity (figure 3A); ovary CD20 (fig 3), CD3 (fig 4); sclerosing; skin (figure 1D); small intestine; unknown site #1-intravascular; #2-sclerosing subtype

other leukemia/lymphoma - follicular lymphoma #1; #2 (childhood); hairy cell leukemia #1; #2-variant type (figure D); Hodgkin’s lymphoma #1-lymphocyte predominant (figures C&D); #2 (figure C); #3-mostly negative Reed-Sternberg cells); lymphoplasmacytic lymphoma/ Waldenström macroglobulinemia #1 (brain-figure D); MALT lymphoma #1 of bladder; #2 of liver; #3 of lung;

SLL of colon (figure C)

post-transplantation lymphoproliferative disorder - #1; #2 (polymorphic subtype-figure C); #3 of liver: H&E, CD20, EBV

other - ectopic hamartomatous thymoma (figure C); lymphocytic mastitis: CD20+/CD3- lymphocytes (B, not T cells); immunoblastic myofibroblastic tumor (figure 2d-reactive B cells)

Additional images: intravascular large cell lymphoma (figure 2a); post-transplant lymphoproliferative disorder

Virtual slides: diffuse large B cell lymphoma

Flow cytometry images: hairy cell leukemia variant - A-CD20 (bright) and CD22+; B-CD11c+ and CD22+; C-CD103+ and CD25 negative; D-CD19+ and FMC7+; E-kappa+; F-lambda negative

Positive staining (normal): most B cells (considered a pan B cell antigen), also follicular dendritic cells

Positive staining (disease): 90% of B cell lymphomas; also B-CLL, hairy cell leukemia, spindle cell thymomas (AJSP 1992;16:988), 40% of pre B ALL/LBL; 80% of nodular lymphocyte predominant Hodgkin’s lymphoma, 20% of classic Hodgkin’s lymphoma (may be an adverse prognostic factor, Br J Haematol 2004;125:701); dimly expressed in T cells (benign and neoplastic, particularly in bone marrow, AJCP 1996;106:78, AJCP 1994;102:483), some myelomas (Mod Path 2004;17:1217, Blood 2003;102:1070)

Negative staining: non-hematopoietic cells, most T cells, plasma cells, mastocytosis

Note: staining does not work well with Bouin’s fixative

Flow cytometry: brighter expression in follicular lymphomas than normal B cells (AJCP 2005;124:576)

References: OMIM 112210, J Biol Chem 2004;279:19893 (presence in lipid rafts)