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An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists


 
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ENIGMATIC MORPHOINSIGHT  
Year : 2020  |  Volume : 24  |  Issue : 3  |  Page : 418-420
 

Tingible body macrophages


Department of Oral Pathology and Microbiology, Subharti Dental College and Hospital, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India

Date of Submission27-Jul-2020
Date of Acceptance06-Oct-2020
Date of Web Publication09-Jan-2021

Correspondence Address:
Suhasini Palakshappa Gotur
Department of Oral Pathology and Microbiology, Subharti Dental College and Hospital, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jomfp.JOMFP_314_2

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How to cite this article:
Gotur SP, Wadhwan V. Tingible body macrophages. J Oral Maxillofac Pathol 2020;24:418-20

How to cite this URL:
Gotur SP, Wadhwan V. Tingible body macrophages. J Oral Maxillofac Pathol [serial online] 2020 [cited 2021 Mar 1];24:418-20. Available from: https://www.jomfp.in/text.asp?2020/24/3/418/306653




Described in 1885 by Flemming, tingible body macrophages (TBMs) represent unique, large phagocytic cells that reside in germinal centers (GCs) of secondary lymphoid tissues and are a subset of mononuclear phagocytes. TBMs contain many phagocytized, apoptotic cells in various states of degradation. They owe their name to their ability to actively phagocytose apoptotic lymphoid cells, and the “tingible bodies” (TBs) observed in their cytoplasm are apoptotic bodies.[1],[2] They are seen scattered among proliferating centroblasts, giving the typical starry-sky appearance to developing GCs.[1],[3]

The closely apposed medium sized tumor cells or the normal lymphocytes in the reactive lymphnodes which have minimal cytoplasm, and a dark nuclei impart a dark blue background (the “sky”) to the histological sections. These cells have a very high turnover rate, so that the nearby macrophages get filled with cellular debris. Upon fixation, the cytoplasm of the macrophages disintegrates, leaving round white spaces filled with debris (the “stars”), imparting a “starry-sky pattern” at low magnification. Nobody knows who created the histological comparison with the “starry-sky” pattern. Perhaps, the unknown author was inspired by the Dutch postimpressionist, Vincent Willem van Gogh's beautiful night paintings.[3]

“Starry-sky pattern” is distinctive for Burkitt lymphoma but can be a nonspecific feature of pronounced follicular hyperplasia seen in bone marrow, lymph node, extranodal mass sections, some thymomas and rheumatoid lymphadenopathy.[3] They may also be observed in other malignant lymphomas with rapid cell turnover, such as precursor B- or T-cell lymphomas and lymphoblastic lymphomas. These high-grade lymphomas, however, often accompany a monomorphic population of atypical lymphoid cells as compared to the polymorphic pattern of small “normal” lymphocytes in reactive conditions.[1] Polarization, normal encompassing mantle zone, absence of bcl-2 positivity, absence of capsular invasion and perinodal fat invasion differentiate the reactive process in lymph nodes from malignancy.[2],[4] The appearance of TBMs and a starry-sky appearance in the paracortex are indicative of increased apoptosis and are suggestive of T-cell production but may also occur with lymphocytolysis.[5] TBMs are also noted in fine-needle aspiration of angiosarcoma of an intraparotid lymph node.[6]

Lymphoid hyperplasia involving both the B-cell-rich follicles and the T-cell-rich paracortex is generally a reactive or immune response and is not considered to be a preneoplastic lesion. Stimulated (reactive) follicles/secondary follicles are usually larger than the unstimulated primary follicles and will have a paler staining GC with large lymphoblasts and increased number of apoptotic lymphocytes and TBMs,[4] as seen in [Figure 1].
Figure 1: Photomicrograph from the reactive submandibular lymph node of an elderly female patient with a large mandibular tumor, histologically diagnosed as follicular ameloblastoma. (a) Capsule, (b) Paracortical germinal center. Tingible body macrophages impart the paracortical germinal center “starry-sky” appearance (H&E, ×10)

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TBMs range in size from 20 to 30 u or larger and contain a variable number of inclusions [Figure 2] and [Figure 3]. Electron microscopically TBMs show the nucleus, 12–15 p in diameter, containing two dense, nucleolar-like areas and peripheral dispersed chromatin. Mitochondria, smooth and rough endoplasmic reticulum and a well-developed Golgi region are present in the macrophage cytoplasm.[7] The inclusions or the phagolysosomes (TBs) represent not only nuclear but also cytoplasmic debris in varying stages of lysis (apoptotic cell debris).[5],[7] Following antigenic stimulation, granulocytes are also seen in TBMs.[7]
Figure 2: Higher magnification of Figure 1, showing (a) tingible body macrophages with intracytoplasmic apoptotic bodies, which represent nuclear debris, surrounded by (b) lymphocytes (H&E, ×40)

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Figure 3: Hand-drawn illustration showing (a) tingible body macrophages with intracytoplasmic apoptotic bodies, surrounded by (b) lymphocytes

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It is generally accepted that the TBMs represent phagocytized debris of small lymphocytes or both lymphocyte and erythrocyte debris. This “graveyard theory” emphasizes the phagocytosis of pyknotic small lymphocytes. This theory was extended by Hamilton, Trowell and Sundberg who postulated reutilization of small lymphocytes in lymphocytopoiesis. Andrew stressed the role of degeneration and phagocytosis of small lymphocytes in GCs as indicating that these centers are not germinal but reactive, contradicting Hellman. Ortega and Mellors suggested that intrinsic GC cells degenerated after secreting gamma globulin and were phagocytized by TBMs. Electron microscopically plasma cell inclusion by TBs is also seen in hyperplastic GCs of lymphatic tissue in the mouse following antigenic stimulation. The plasma cell phagocytosis by TBMs may reflect plasma cell proliferation rather than lymphocyte production from the population of cells comprising GCs after antigenic stimulation. This proposal is in agreement with the suggestion by Ringertz and Adamson and Congdon and Goodman that the centers form either antibody-producing plasma cells or lymphocytes, depending on an antigenic stimulus. This idea is also consistent with the functional proposal by Ortega and Mellors that depleted GC cells are phagocytized following protein synthetic activity.[7]

Unique to TBMs is the GC microenvironment, characterized functionally by long-term antigen retention on follicular dendritic cells, antigen presentation by B-cells to T-helper cells, a high rate of somatic mutations, affinity maturation, induction of antibody-forming cells and memory B-cell development. Apart from the scavenging function, TBMs also may be important in initiating the GC reaction. This suggestion was based on the observations that TBM initially appeared at the onset of GC development and that a peak number of TBMs were seen at peak GC development. However, it has been shown that GCs can develop in old mice in the absence of TBM. This advocates a regulatory role of TBM and that TBMs are more likely to downregulate than to stimulate the GC reaction.[8] Further, TBMs were found to be rich in prostaglandins via which they downregulate the GC reaction.[2],[9]

It has been suggested that the scavenging activity of TBM may play a significant role in preventing autoimmunity.[2] Fat globule-epidermal growth factor 8 (Mfge8) promotes TBMs to engulf apoptotic bodies in GCs and helps minimize autoimmunity.[9] Furthermore, this is illustrated by a confocal microscopic study of TBMs, to evaluate the in vivo capacity to remove apoptotic cell material, conducted on patients with systemic lupus erythematosus (SLE). In lymph nodes GCs from the patients with SLE, the apoptotic cells were more and the TBMs were reduced in number, in contrast to the control group. This finding suggested that in SLE patients, apoptotic cells are not properly cleared by TBMs. Consequently, retained nuclear autoantigens can be presented to and bind to follicular dendritic cells and may thus provide survival signals for autoreactive B-cells, thereby initiating or propagating autoimmune disease.[2],[10]

To conclude, TBMs in GCs of reactive lymph nodes represent a benign process which should be differentiated from the lymphomas and other malignancies. Further studies are required to understand the role of TBMs in the pathogenesis of various autoimmune diseases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Tingible Body Macrophage - an overview _ ScienceDirect Topics. Available from: https://www.sciencedirect.com/topics/ biochemistry genetics and molecular biology/tingible body macrophage. [Last accessed on 2020 May 30].  Back to cited text no. 1
    
2.
North JP, McCalmont TH. Angiosarcoma with tingible body macrophages. J Cutan Pathol 2011;38:683.  Back to cited text no. 2
    
3.
Andrade-Filho Jde S. Analogies in medicine: Starry-sky appearance. Rev Inst Med Trop Sao Paulo 2014;56:541-2.  Back to cited text no. 3
    
4.
Elmore SA. Histopathology of the lymph nodes. Toxicol Pathol 2006;34:425-54.  Back to cited text no. 4
    
5.
Willard-Mack CL. Normal structure, function, and histology of lymph nodes. Toxicol Pathol 2006;34:409-24.  Back to cited text no. 5
    
6.
Ducharne-Asuaje E, Dorion D, Lamarre L, Coindre JM, Geha S. Primary high-grade poorly differentiated angiosarcoma of an intra-parotid lymph node. Head Neck Pathol 2016;10:225-8.  Back to cited text no. 6
    
7.
Swartzendruber DC, Congdon CC. Electron microscope observations on tingible body macrophages in mouse spleen. J Cell Biol 1963;19:641-6.  Back to cited text no. 7
    
8.
Smith JP, Burton GF, Tew JG, Szakal AK. Tingible body macrophages in regulation of germinal center reactions. Dev Immunol 1998;6:285-94.  Back to cited text no. 8
    
9.
El Shikh ME, Pitzalis C. Follicular dendritic cells in health and disease. Front Immunol 2012;3:292.  Back to cited text no. 9
    
10.
Baumann I, Kolowos W, Voll RE, Manger B, Gaipl U, Neuhuber WL, et al. Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum 2002;46:191-201.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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